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Published in: Virology Journal 1/2013

Open Access 01-12-2013 | Research

Combination of autophagy inducer rapamycin and oncolytic adenovirus improves antitumor effect in cancer cells

Authors: Pei-Hsin Cheng, Serena Lian, Robin Zhao, Xiao-Mei Rao, Kelly M McMasters, Heshan Sam Zhou

Published in: Virology Journal | Issue 1/2013

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Abstract

Background

Combination of oncolytic adenoviruses (Ads) and chemotherapy drugs has shown promising therapeutic results and is considered as a potential approach for cancer therapy. We previously have shown that autophagy may generate decomposed cellular molecules that can be used as nutrition to support virus replication in cancer cells. In this study, we evaluated a unique combination of the novel oncolytic Ad-cycE with rapamycin, an autophagy inducer and first-line chemotherapeutic drug.

Methods

The combination of oncolytic Ad-cycE and the autophagy inducer rapamycin was assessed for enhanced antitumor effect. We also evaluated the combined effects of rapamycin and Ad-cycE on cancer cell viability. The interaction between Ad-cycE and rapamycin was analyzed with Calcusyn (Biosoft, Ferguson, MO).

Results

We show that rapamycin induces autophagy, enhances Ad E1A expression and increases Ad oncolytic replication. Combination of rapamycin and Ad-cycE elicits stronger cytotoxicity than single treatment alone. The analyzed data indicates that the Ad-cycE and rapamycin combination has a significantly synergistic antitumor effect.

Conclusions

Our study provides a new insight into vector development and demonstrates the novel roles of autophagy in adenovirus replication. The combination of autophagy-induced chemotherapy and oncolytic virotherapy may be a new approach to improve future cancer treatment.
Appendix
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Literature
1.
go back to reference Yu W, Fang H: Clinical trials with oncolytic adenovirus in China. Curr Cancer Drug Targets 2007, 7: 141-148. 10.2174/156800907780058817PubMedCrossRef Yu W, Fang H: Clinical trials with oncolytic adenovirus in China. Curr Cancer Drug Targets 2007, 7: 141-148. 10.2174/156800907780058817PubMedCrossRef
2.
go back to reference Eager RM, Nemunaitis J: Clinical development directions in oncolytic viral therapy. Cancer Gene Ther 2011, 18: 305-317. 10.1038/cgt.2011.7PubMedCrossRef Eager RM, Nemunaitis J: Clinical development directions in oncolytic viral therapy. Cancer Gene Ther 2011, 18: 305-317. 10.1038/cgt.2011.7PubMedCrossRef
3.
go back to reference Kim KH, Ryan MJ, Estep JE, Miniard BM, Rudge TL, Peggins JO, Broadt TL, Wang M, Preuss MA, Siegal GP, et al.: A new generation of serotype chimeric infectivity-enhanced conditionally replicative adenovirals: the safety profile of ad5/3-Delta24 in advance of a phase I clinical trial in ovarian cancer patients. Hum Gene Ther 2011, 22: 821-828. 10.1089/hum.2010.180PubMedPubMedCentralCrossRef Kim KH, Ryan MJ, Estep JE, Miniard BM, Rudge TL, Peggins JO, Broadt TL, Wang M, Preuss MA, Siegal GP, et al.: A new generation of serotype chimeric infectivity-enhanced conditionally replicative adenovirals: the safety profile of ad5/3-Delta24 in advance of a phase I clinical trial in ovarian cancer patients. Hum Gene Ther 2011, 22: 821-828. 10.1089/hum.2010.180PubMedPubMedCentralCrossRef
4.
go back to reference Nemunaitis J, Tong AW, Nemunaitis M, Senzer N, Phadke AP, Bedell C, Adams N, Zhang YA, Maples PB, Chen S, et al.: A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors. Mol Ther 2010, 18: 429-434. 10.1038/mt.2009.262PubMedPubMedCentralCrossRef Nemunaitis J, Tong AW, Nemunaitis M, Senzer N, Phadke AP, Bedell C, Adams N, Zhang YA, Maples PB, Chen S, et al.: A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors. Mol Ther 2010, 18: 429-434. 10.1038/mt.2009.262PubMedPubMedCentralCrossRef
5.
go back to reference Kimball KJ, Preuss MA, Barnes MN, Wang M, Siegal GP, Wan W, Kuo H, Saddekni S, Stockard CR, Grizzle WE, et al.: A phase I study of a tropism-modified conditionally replicative adenovirus for recurrent malignant gynecologic diseases. Clin Cancer Res 2010, 16: 5277-5287. 10.1158/1078-0432.CCR-10-0791PubMedPubMedCentralCrossRef Kimball KJ, Preuss MA, Barnes MN, Wang M, Siegal GP, Wan W, Kuo H, Saddekni S, Stockard CR, Grizzle WE, et al.: A phase I study of a tropism-modified conditionally replicative adenovirus for recurrent malignant gynecologic diseases. Clin Cancer Res 2010, 16: 5277-5287. 10.1158/1078-0432.CCR-10-0791PubMedPubMedCentralCrossRef
6.
7.
go back to reference Wold WS, Toth K: Chapter three–Syrian hamster as an animal model to study oncolytic adenoviruses and to evaluate the efficacy of antiviral compounds. Adv Cancer Res 2012, 115: 69-92.PubMedCrossRef Wold WS, Toth K: Chapter three–Syrian hamster as an animal model to study oncolytic adenoviruses and to evaluate the efficacy of antiviral compounds. Adv Cancer Res 2012, 115: 69-92.PubMedCrossRef
8.
go back to reference Waszak P, Franco-Montoya ML, Jacob MP, Deprez I, Levame M, Lafuma C, Harf A, Delacourt C: Effect of intratracheal adenoviral vector administration on lung development in newborn rats. Hum Gene Ther 2002, 13: 1873-1885. 10.1089/104303402760372963PubMedCrossRef Waszak P, Franco-Montoya ML, Jacob MP, Deprez I, Levame M, Lafuma C, Harf A, Delacourt C: Effect of intratracheal adenoviral vector administration on lung development in newborn rats. Hum Gene Ther 2002, 13: 1873-1885. 10.1089/104303402760372963PubMedCrossRef
9.
go back to reference Ottolino-Perry K, Diallo JS, Lichty BD, Bell JC, McCart JA: Intelligent design: combination therapy with oncolytic viruses. Mol Ther 2010, 18: 251-263. 10.1038/mt.2009.283PubMedPubMedCentralCrossRef Ottolino-Perry K, Diallo JS, Lichty BD, Bell JC, McCart JA: Intelligent design: combination therapy with oncolytic viruses. Mol Ther 2010, 18: 251-263. 10.1038/mt.2009.283PubMedPubMedCentralCrossRef
10.
go back to reference Rodriguez-Rocha H, Gomez-Gutierrez JG, Garcia-Garcia A, Rao XM, Chen L, McMasters KM, Zhou HS: Adenoviruses induce autophagy to promote virus replication and oncolysis. Virology 2011, 416: 9-15. 10.1016/j.virol.2011.04.017PubMedPubMedCentralCrossRef Rodriguez-Rocha H, Gomez-Gutierrez JG, Garcia-Garcia A, Rao XM, Chen L, McMasters KM, Zhou HS: Adenoviruses induce autophagy to promote virus replication and oncolysis. Virology 2011, 416: 9-15. 10.1016/j.virol.2011.04.017PubMedPubMedCentralCrossRef
11.
go back to reference Kondo Y, Kanzawa T, Sawaya R, Kondo S: The role of autophagy in cancer development and response to therapy. Nat Rev Cancer 2005, 5: 726-734. 10.1038/nrc1692PubMedCrossRef Kondo Y, Kanzawa T, Sawaya R, Kondo S: The role of autophagy in cancer development and response to therapy. Nat Rev Cancer 2005, 5: 726-734. 10.1038/nrc1692PubMedCrossRef
12.
go back to reference Stromhaug PE, Berg TO, Fengsrud M, Seglen PO: Purification and characterization of autophagosomes from rat hepatocytes. Biochem J 1998,335(Pt 2):217-224.PubMedPubMedCentralCrossRef Stromhaug PE, Berg TO, Fengsrud M, Seglen PO: Purification and characterization of autophagosomes from rat hepatocytes. Biochem J 1998,335(Pt 2):217-224.PubMedPubMedCentralCrossRef
13.
go back to reference Chen Y, Azad MB, Gibson SB: Methods for detecting autophagy and determining autophagy-induced cell death. Can J Physiol Pharmacol 2010, 88: 285-295. 10.1139/Y10-010PubMedCrossRef Chen Y, Azad MB, Gibson SB: Methods for detecting autophagy and determining autophagy-induced cell death. Can J Physiol Pharmacol 2010, 88: 285-295. 10.1139/Y10-010PubMedCrossRef
14.
go back to reference Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T: LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000, 19: 5720-5728. 10.1093/emboj/19.21.5720PubMedPubMedCentralCrossRef Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T: LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000, 19: 5720-5728. 10.1093/emboj/19.21.5720PubMedPubMedCentralCrossRef
15.
go back to reference Mizushima N: Methods for monitoring autophagy. Int J Biochem Cell Biol 2004, 36: 2491-2502. 10.1016/j.biocel.2004.02.005PubMedCrossRef Mizushima N: Methods for monitoring autophagy. Int J Biochem Cell Biol 2004, 36: 2491-2502. 10.1016/j.biocel.2004.02.005PubMedCrossRef
16.
17.
go back to reference Kim HJ, Lee S, Jung JU: When autophagy meets viruses: a double-edged sword with functions in defense and offense. Semin Immunopathol 2010, 32: 323-341. 10.1007/s00281-010-0226-8PubMedPubMedCentralCrossRef Kim HJ, Lee S, Jung JU: When autophagy meets viruses: a double-edged sword with functions in defense and offense. Semin Immunopathol 2010, 32: 323-341. 10.1007/s00281-010-0226-8PubMedPubMedCentralCrossRef
19.
go back to reference Sarbassov DD, Ali SM, Sabatini DM: Growing roles for the mTOR pathway. Curr Opin Cell Biol 2005, 17: 596-603. 10.1016/j.ceb.2005.09.009PubMedCrossRef Sarbassov DD, Ali SM, Sabatini DM: Growing roles for the mTOR pathway. Curr Opin Cell Biol 2005, 17: 596-603. 10.1016/j.ceb.2005.09.009PubMedCrossRef
20.
go back to reference Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM: Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006, 22: 159-168. 10.1016/j.molcel.2006.03.029PubMedCrossRef Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM: Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006, 22: 159-168. 10.1016/j.molcel.2006.03.029PubMedCrossRef
21.
go back to reference Takeuchi H, Kondo Y, Fujiwara K, Kanzawa T, Aoki H, Mills GB, Kondo S: Synergistic augmentation of rapamycin-induced autophagy in malignant glioma cells by phosphatidylinositol 3-kinase/protein kinase B inhibitors. Cancer Res 2005, 65: 3336-3346.PubMed Takeuchi H, Kondo Y, Fujiwara K, Kanzawa T, Aoki H, Mills GB, Kondo S: Synergistic augmentation of rapamycin-induced autophagy in malignant glioma cells by phosphatidylinositol 3-kinase/protein kinase B inhibitors. Cancer Res 2005, 65: 3336-3346.PubMed
22.
go back to reference Ben-Israel H, Kleinberger T: Adenovirus and cell cycle control. Front Biosci 2002, 7: d1369-1395. 10.2741/benPubMedCrossRef Ben-Israel H, Kleinberger T: Adenovirus and cell cycle control. Front Biosci 2002, 7: d1369-1395. 10.2741/benPubMedCrossRef
23.
go back to reference Davis JJ, Wang L, Dong F, Zhang L, Guo W, Teraishi F, Xu K, Ji L, Fang B: Oncolysis and suppression of tumor growth by a GFP-expressing oncolytic adenovirus controlled by an hTERT and CMV hybrid promoter. Cancer Gene Ther 2006, 13: 720-723. 10.1038/sj.cgt.7700944PubMedPubMedCentralCrossRef Davis JJ, Wang L, Dong F, Zhang L, Guo W, Teraishi F, Xu K, Ji L, Fang B: Oncolysis and suppression of tumor growth by a GFP-expressing oncolytic adenovirus controlled by an hTERT and CMV hybrid promoter. Cancer Gene Ther 2006, 13: 720-723. 10.1038/sj.cgt.7700944PubMedPubMedCentralCrossRef
24.
go back to reference Fu X, Meng F, Tao L, Jin A, Zhang X: A strict-late viral promoter is a strong tumor-specific promoter in the context of an oncolytic herpes simplex virus. Gene Ther 2003, 10: 1458-1464. 10.1038/sj.gt.3302029PubMedCrossRef Fu X, Meng F, Tao L, Jin A, Zhang X: A strict-late viral promoter is a strong tumor-specific promoter in the context of an oncolytic herpes simplex virus. Gene Ther 2003, 10: 1458-1464. 10.1038/sj.gt.3302029PubMedCrossRef
25.
go back to reference Rao XM, Zheng X, Waigel S, Zacharias W, McMasters KM, Zhou HS: Gene expression profiles of normal human lung cells affected by adenoviral E1B. Virology 2006, 350: 418-428. 10.1016/j.virol.2006.02.009PubMedCrossRef Rao XM, Zheng X, Waigel S, Zacharias W, McMasters KM, Zhou HS: Gene expression profiles of normal human lung cells affected by adenoviral E1B. Virology 2006, 350: 418-428. 10.1016/j.virol.2006.02.009PubMedCrossRef
26.
go back to reference Toth K, Dhar D, Wold WS: Oncolytic (replication-competent) adenoviruses as anticancer agents. Expert Opin Biol Ther 2010, 10: 353-368. 10.1517/14712590903559822PubMedCrossRef Toth K, Dhar D, Wold WS: Oncolytic (replication-competent) adenoviruses as anticancer agents. Expert Opin Biol Ther 2010, 10: 353-368. 10.1517/14712590903559822PubMedCrossRef
27.
go back to reference Kurihara T, Brough DE, Kovesdi I, Kufe DW: Selectivity of a replication-competent adenovirus for human breast carcinoma cells expressing the MUC1 antigen. J Clin Invest 2000, 106: 763-771. 10.1172/JCI9180PubMedPubMedCentralCrossRef Kurihara T, Brough DE, Kovesdi I, Kufe DW: Selectivity of a replication-competent adenovirus for human breast carcinoma cells expressing the MUC1 antigen. J Clin Invest 2000, 106: 763-771. 10.1172/JCI9180PubMedPubMedCentralCrossRef
28.
go back to reference Coverley D, Laman H, Laskey RA: Distinct roles for cyclins E and A during DNA replication complex assembly and activation. Nat Cell Biol 2002, 4: 523-528. 10.1038/ncb813PubMedCrossRef Coverley D, Laman H, Laskey RA: Distinct roles for cyclins E and A during DNA replication complex assembly and activation. Nat Cell Biol 2002, 4: 523-528. 10.1038/ncb813PubMedCrossRef
29.
go back to reference Furstenthal L, Kaiser BK, Swanson C, Jackson PK: Cyclin E uses Cdc6 as a chromatin-associated receptor required for DNA replication. J Cell Biol 2001, 152: 1267-1278. 10.1083/jcb.152.6.1267PubMedPubMedCentralCrossRef Furstenthal L, Kaiser BK, Swanson C, Jackson PK: Cyclin E uses Cdc6 as a chromatin-associated receptor required for DNA replication. J Cell Biol 2001, 152: 1267-1278. 10.1083/jcb.152.6.1267PubMedPubMedCentralCrossRef
30.
go back to reference Donnellan R, Chetty R: Cyclin E in human cancers. FASEB J 1999, 13: 773-780.PubMed Donnellan R, Chetty R: Cyclin E in human cancers. FASEB J 1999, 13: 773-780.PubMed
31.
go back to reference Loeb KR, Kostner H, Firpo E, Norwood T, DTsuchiya K, Clurman BE, Roberts JM: A mouse model for cyclin E-dependent genetic instability and tumorigenesis. Cancer Cell 2005, 8: 35-47. 10.1016/j.ccr.2005.06.010PubMedCrossRef Loeb KR, Kostner H, Firpo E, Norwood T, DTsuchiya K, Clurman BE, Roberts JM: A mouse model for cyclin E-dependent genetic instability and tumorigenesis. Cancer Cell 2005, 8: 35-47. 10.1016/j.ccr.2005.06.010PubMedCrossRef
32.
go back to reference Freemantle SJ, Dmitrovsky E: Cyclin E transgenic mice: discovery tools for lung cancer biology, therapy, and prevention. Cancer Prev Res (Phila) 2010, 3: 1513-1518. 10.1158/1940-6207.CAPR-10-0297CrossRef Freemantle SJ, Dmitrovsky E: Cyclin E transgenic mice: discovery tools for lung cancer biology, therapy, and prevention. Cancer Prev Res (Phila) 2010, 3: 1513-1518. 10.1158/1940-6207.CAPR-10-0297CrossRef
33.
go back to reference Zheng X, Rao XM, Gomez-Gutierrez JG, Hao H, McMasters KM, Zhou HS: Adenovirus E1B55K region is required to enhance cyclin E expression for efficient viral DNA replication. J Virol 2008, 82: 3415-3427. 10.1128/JVI.01708-07PubMedPubMedCentralCrossRef Zheng X, Rao XM, Gomez-Gutierrez JG, Hao H, McMasters KM, Zhou HS: Adenovirus E1B55K region is required to enhance cyclin E expression for efficient viral DNA replication. J Virol 2008, 82: 3415-3427. 10.1128/JVI.01708-07PubMedPubMedCentralCrossRef
34.
go back to reference Zheng X, Rao XM, Snodgrass CL, McMasters KM, Zhou HS: Selective replication of E1B55K-deleted adenoviruses depends on enhanced E1A expression in cancer cells. Cancer Gene Ther 2006, 13: 572-583. 10.1038/sj.cgt.7700923PubMedCrossRef Zheng X, Rao XM, Snodgrass CL, McMasters KM, Zhou HS: Selective replication of E1B55K-deleted adenoviruses depends on enhanced E1A expression in cancer cells. Cancer Gene Ther 2006, 13: 572-583. 10.1038/sj.cgt.7700923PubMedCrossRef
35.
go back to reference Gomez-Gutierrez JG, Rao XM, Zhou HS, McMasters KM: Enhanced cancer cell killing by truncated E2F-1 used in combination with oncolytic adenovirus. Virology 2012, 433: 538-547. 10.1016/j.virol.2012.09.003PubMedPubMedCentralCrossRef Gomez-Gutierrez JG, Rao XM, Zhou HS, McMasters KM: Enhanced cancer cell killing by truncated E2F-1 used in combination with oncolytic adenovirus. Virology 2012, 433: 538-547. 10.1016/j.virol.2012.09.003PubMedPubMedCentralCrossRef
36.
go back to reference Hayflick L: The Limited in Vitro Lifetime of Human Diploid Cell Strains. Exp Cell Res 1965, 37: 614-636. 10.1016/0014-4827(65)90211-9PubMedCrossRef Hayflick L: The Limited in Vitro Lifetime of Human Diploid Cell Strains. Exp Cell Res 1965, 37: 614-636. 10.1016/0014-4827(65)90211-9PubMedCrossRef
37.
go back to reference Khanna S, Darbre PD: Parabens enable suspension growth of MCF-10A immortalized, non-transformed human breast epithelial cells. J Appl Toxicol 2013, 33: 378-382. 10.1002/jat.2753PubMedCrossRef Khanna S, Darbre PD: Parabens enable suspension growth of MCF-10A immortalized, non-transformed human breast epithelial cells. J Appl Toxicol 2013, 33: 378-382. 10.1002/jat.2753PubMedCrossRef
38.
go back to reference Soule HD, Maloney TM, Wolman SR, Peterson WD Jr, Brenz R, McGrath CM, Russo J, Pauley RJ, Jones RF, Brooks SC: Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res 1990, 50: 6075-6086.PubMed Soule HD, Maloney TM, Wolman SR, Peterson WD Jr, Brenz R, McGrath CM, Russo J, Pauley RJ, Jones RF, Brooks SC: Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res 1990, 50: 6075-6086.PubMed
39.
go back to reference Cheng PH, Rao XM, McMasters KM, Zhou HS: Molecular basis for viral selective replication in cancer cells: activation of CDK2 by adenovirus-induced cyclin E. PLoS One 2013, 8: e57340. 10.1371/journal.pone.0057340PubMedPubMedCentralCrossRef Cheng PH, Rao XM, McMasters KM, Zhou HS: Molecular basis for viral selective replication in cancer cells: activation of CDK2 by adenovirus-induced cyclin E. PLoS One 2013, 8: e57340. 10.1371/journal.pone.0057340PubMedPubMedCentralCrossRef
40.
go back to reference Geng Y, Eaton EN, Picon M, Roberts JM, Lundberg AS, Gifford A, Sardet C, Weinberg RA: Regulation of cyclin E transcription by E2Fs and retinoblastoma protein. Oncogene 1996, 12: 1173-1180.PubMed Geng Y, Eaton EN, Picon M, Roberts JM, Lundberg AS, Gifford A, Sardet C, Weinberg RA: Regulation of cyclin E transcription by E2Fs and retinoblastoma protein. Oncogene 1996, 12: 1173-1180.PubMed
41.
go back to reference Ishiyama M, Tominaga H, Shiga M, Sasamoto K, Ohkura Y, Ueno K: A combined assay of cell viability and in vitro cytotoxicity with a highly water-soluble tetrazolium salt, neutral red and crystal violet. Biol Pharm Bull 1996, 19: 1518-1520. 10.1248/bpb.19.1518PubMedCrossRef Ishiyama M, Tominaga H, Shiga M, Sasamoto K, Ohkura Y, Ueno K: A combined assay of cell viability and in vitro cytotoxicity with a highly water-soluble tetrazolium salt, neutral red and crystal violet. Biol Pharm Bull 1996, 19: 1518-1520. 10.1248/bpb.19.1518PubMedCrossRef
42.
go back to reference Kwon OJ, Kim PH, Huyn S, Wu L, Kim M, Yun CO: A hypoxia- and {alpha}-fetoprotein-dependent oncolytic adenovirus exhibits specific killing of hepatocellular carcinomas. Clin Cancer Res 2010, 16: 6071-6082. 10.1158/1078-0432.CCR-10-0664PubMedCrossRef Kwon OJ, Kim PH, Huyn S, Wu L, Kim M, Yun CO: A hypoxia- and {alpha}-fetoprotein-dependent oncolytic adenovirus exhibits specific killing of hepatocellular carcinomas. Clin Cancer Res 2010, 16: 6071-6082. 10.1158/1078-0432.CCR-10-0664PubMedCrossRef
43.
go back to reference Wang S, Meckling KA, Marcone MF, Kakuda Y, Tsao R: Synergistic, additive, and antagonistic effects of food mixtures on total antioxidant capacities. J Agric Food Chem 2011, 59: 960-968. 10.1021/jf1040977PubMedCrossRef Wang S, Meckling KA, Marcone MF, Kakuda Y, Tsao R: Synergistic, additive, and antagonistic effects of food mixtures on total antioxidant capacities. J Agric Food Chem 2011, 59: 960-968. 10.1021/jf1040977PubMedCrossRef
44.
go back to reference Chou TC: Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 2006, 58: 621-681. 10.1124/pr.58.3.10PubMedCrossRef Chou TC: Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 2006, 58: 621-681. 10.1124/pr.58.3.10PubMedCrossRef
45.
go back to reference Chou TC, Talalay P: Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984, 22: 27-55.PubMedCrossRef Chou TC, Talalay P: Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984, 22: 27-55.PubMedCrossRef
46.
go back to reference Steel GG, Peckham MJ: Exploitable mechanisms in combined radiotherapy-chemotherapy: the concept of additivity. Int J Radiat Oncol Biol Phys 1979, 5: 85-91.PubMedCrossRef Steel GG, Peckham MJ: Exploitable mechanisms in combined radiotherapy-chemotherapy: the concept of additivity. Int J Radiat Oncol Biol Phys 1979, 5: 85-91.PubMedCrossRef
47.
go back to reference Niu C, Bao H, Tolstykh T, Micolochick Steuer HM, Murakami E, Korba B, Furman PA: Evaluation of the in vitro anti-HBV activity of clevudine in combination with other nucleoside/nucleotide inhibitors. Antivir Ther 2010, 15: 401-412. 10.3851/IMP1541PubMedCrossRef Niu C, Bao H, Tolstykh T, Micolochick Steuer HM, Murakami E, Korba B, Furman PA: Evaluation of the in vitro anti-HBV activity of clevudine in combination with other nucleoside/nucleotide inhibitors. Antivir Ther 2010, 15: 401-412. 10.3851/IMP1541PubMedCrossRef
48.
go back to reference Sandig V, Youil R, Bett AJ, Franlin LL, Oshima M, Maione D, Wang F, Metzker ML, Savino R, Caskey CT: Optimization of the helper-dependent adenovirus system for production and potency in vivo. Proc Natl Acad Sci U S A 2000, 97: 1002-1007. 10.1073/pnas.97.3.1002PubMedPubMedCentralCrossRef Sandig V, Youil R, Bett AJ, Franlin LL, Oshima M, Maione D, Wang F, Metzker ML, Savino R, Caskey CT: Optimization of the helper-dependent adenovirus system for production and potency in vivo. Proc Natl Acad Sci U S A 2000, 97: 1002-1007. 10.1073/pnas.97.3.1002PubMedPubMedCentralCrossRef
49.
go back to reference Zhao T, Rao XM, Xie X, Li L, Thompson TC, McMasters KM, Zhou HS: Adenovirus with insertion-mutated E1A selectively propagates in liver cancer cells and destroys tumors in vivo. Cancer Res 2003, 63: 3073-3078.PubMed Zhao T, Rao XM, Xie X, Li L, Thompson TC, McMasters KM, Zhou HS: Adenovirus with insertion-mutated E1A selectively propagates in liver cancer cells and destroys tumors in vivo. Cancer Res 2003, 63: 3073-3078.PubMed
50.
go back to reference D'Avenia P, Porrello A, Berardo M, Angelo MD, Soddu S, Arcangeli G, Sacchi A, D'Orazi G: Tp53-gene transfer induces hypersensitivity to low doses of X-rays in glioblastoma cells: a strategy to convert a radio-resistant phenotype into a radiosensitive one. Cancer Lett 2006, 231: 102-112. 10.1016/j.canlet.2005.01.033PubMedCrossRef D'Avenia P, Porrello A, Berardo M, Angelo MD, Soddu S, Arcangeli G, Sacchi A, D'Orazi G: Tp53-gene transfer induces hypersensitivity to low doses of X-rays in glioblastoma cells: a strategy to convert a radio-resistant phenotype into a radiosensitive one. Cancer Lett 2006, 231: 102-112. 10.1016/j.canlet.2005.01.033PubMedCrossRef
51.
go back to reference Pinto-Leite R, Botelho P, Ribeiro E, Oliveira PA, Santos L: Effect of sirolimus on urinary bladder cancer T24 cell line. J Exp Clin Cancer Res 2009, 28: 3. 10.1186/1756-9966-28-3PubMedPubMedCentralCrossRef Pinto-Leite R, Botelho P, Ribeiro E, Oliveira PA, Santos L: Effect of sirolimus on urinary bladder cancer T24 cell line. J Exp Clin Cancer Res 2009, 28: 3. 10.1186/1756-9966-28-3PubMedPubMedCentralCrossRef
52.
go back to reference Lee CT, Park KH, Yanagisawa K, Adachi Y, Ohm JE, Nadaf S, Dikov MM, Curiel DT, Carbone DP: Combination therapy with conditionally replicating adenovirus and replication defective adenovirus. Cancer Res 2004, 64: 6660-6665. 10.1158/0008-5472.CAN-04-1200PubMedCrossRef Lee CT, Park KH, Yanagisawa K, Adachi Y, Ohm JE, Nadaf S, Dikov MM, Curiel DT, Carbone DP: Combination therapy with conditionally replicating adenovirus and replication defective adenovirus. Cancer Res 2004, 64: 6660-6665. 10.1158/0008-5472.CAN-04-1200PubMedCrossRef
53.
go back to reference Lee CT, Lee YJ, Kwon SY, Lee J, Kim KI, Park KH, Kang JH, Yoo CG, Kim YW, Han SK, et al.: In vivo imaging of adenovirus transduction and enhanced therapeutic efficacy of combination therapy with conditionally replicating adenovirus and adenovirus-p27. Cancer Res 2006, 66: 372-377. 10.1158/0008-5472.CAN-05-1515PubMedCrossRef Lee CT, Lee YJ, Kwon SY, Lee J, Kim KI, Park KH, Kang JH, Yoo CG, Kim YW, Han SK, et al.: In vivo imaging of adenovirus transduction and enhanced therapeutic efficacy of combination therapy with conditionally replicating adenovirus and adenovirus-p27. Cancer Res 2006, 66: 372-377. 10.1158/0008-5472.CAN-05-1515PubMedCrossRef
54.
go back to reference Harlow E, Franza BR Jr, Schley C: Monoclonal antibodies specific for adenovirus early region 1A proteins: extensive heterogeneity in early region 1A products. J Virol 1985, 55: 533-546.PubMedPubMedCentral Harlow E, Franza BR Jr, Schley C: Monoclonal antibodies specific for adenovirus early region 1A proteins: extensive heterogeneity in early region 1A products. J Virol 1985, 55: 533-546.PubMedPubMedCentral
55.
go back to reference Chou TC, Talalay P: Generalized equations for the analysis of inhibitions of Michaelis-Menten and higher-order kinetic systems with two or more mutually exclusive and nonexclusive inhibitors. Eur J Biochem 1981, 115: 207-216.PubMedCrossRef Chou TC, Talalay P: Generalized equations for the analysis of inhibitions of Michaelis-Menten and higher-order kinetic systems with two or more mutually exclusive and nonexclusive inhibitors. Eur J Biochem 1981, 115: 207-216.PubMedCrossRef
56.
go back to reference Vaha-Koskela MJ, Heikkila JE, Hinkkanen AE: Oncolytic viruses in cancer therapy. Cancer Lett 2007, 254: 178-216. 10.1016/j.canlet.2007.02.002PubMedCrossRef Vaha-Koskela MJ, Heikkila JE, Hinkkanen AE: Oncolytic viruses in cancer therapy. Cancer Lett 2007, 254: 178-216. 10.1016/j.canlet.2007.02.002PubMedCrossRef
57.
go back to reference Kirn D: Clinical research results with dl1520 (Onyx-015), a replication-selective adenovirus for the treatment of cancer: what have we learned? Gene Ther 2001, 8: 89-98. 10.1038/sj.gt.3301377PubMedCrossRef Kirn D: Clinical research results with dl1520 (Onyx-015), a replication-selective adenovirus for the treatment of cancer: what have we learned? Gene Ther 2001, 8: 89-98. 10.1038/sj.gt.3301377PubMedCrossRef
59.
go back to reference Zeng X, Carlin CR: Host cell autophagy modulates early stages of adenovirus infections in airway epithelial cells. J Virol 2013, 87: 2307-2319. 10.1128/JVI.02014-12PubMedPubMedCentralCrossRef Zeng X, Carlin CR: Host cell autophagy modulates early stages of adenovirus infections in airway epithelial cells. J Virol 2013, 87: 2307-2319. 10.1128/JVI.02014-12PubMedPubMedCentralCrossRef
60.
go back to reference Randow F, Munz C: Autophagy in the regulation of pathogen replication and adaptive immunity. Trends Immunol 2012, 33: 475-487. 10.1016/j.it.2012.06.003PubMedPubMedCentralCrossRef Randow F, Munz C: Autophagy in the regulation of pathogen replication and adaptive immunity. Trends Immunol 2012, 33: 475-487. 10.1016/j.it.2012.06.003PubMedPubMedCentralCrossRef
61.
go back to reference Saunders RN, Metcalfe MS, Nicholson ML: Rapamycin in transplantation: a review of the evidence. Kidney Int 2001, 59: 3-16. 10.1046/j.1523-1755.2001.00460.xPubMedCrossRef Saunders RN, Metcalfe MS, Nicholson ML: Rapamycin in transplantation: a review of the evidence. Kidney Int 2001, 59: 3-16. 10.1046/j.1523-1755.2001.00460.xPubMedCrossRef
62.
go back to reference Moretti L, Yang ES, Kim KW, Lu B: Autophagy signaling in cancer and its potential as novel target to improve anticancer therapy. Drug Resist Updat 2007, 10: 135-143. 10.1016/j.drup.2007.05.001PubMedCrossRef Moretti L, Yang ES, Kim KW, Lu B: Autophagy signaling in cancer and its potential as novel target to improve anticancer therapy. Drug Resist Updat 2007, 10: 135-143. 10.1016/j.drup.2007.05.001PubMedCrossRef
63.
go back to reference Sir D, Tian Y, Chen WL, Ann DK, Yen TS, Ou JH: The early autophagic pathway is activated by hepatitis B virus and required for viral DNA replication. Proc Natl Acad Sci U S A 2010, 107: 4383-4388. 10.1073/pnas.0911373107PubMedPubMedCentralCrossRef Sir D, Tian Y, Chen WL, Ann DK, Yen TS, Ou JH: The early autophagic pathway is activated by hepatitis B virus and required for viral DNA replication. Proc Natl Acad Sci U S A 2010, 107: 4383-4388. 10.1073/pnas.0911373107PubMedPubMedCentralCrossRef
64.
go back to reference Dreux M, Gastaminza P, Wieland SF, Chisari FV: The autophagy machinery is required to initiate hepatitis C virus replication. Proc Natl Acad Sci U S A 2009, 106: 14046-14051. 10.1073/pnas.0907344106PubMedPubMedCentralCrossRef Dreux M, Gastaminza P, Wieland SF, Chisari FV: The autophagy machinery is required to initiate hepatitis C virus replication. Proc Natl Acad Sci U S A 2009, 106: 14046-14051. 10.1073/pnas.0907344106PubMedPubMedCentralCrossRef
65.
go back to reference Jackson WT, Giddings TH Jr, Taylor MP, Mulinyawe S, Rabinovitch M, Kopito RR, Kirkegaard K: Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol 2005, 3: e156. 10.1371/journal.pbio.0030156PubMedPubMedCentralCrossRef Jackson WT, Giddings TH Jr, Taylor MP, Mulinyawe S, Rabinovitch M, Kopito RR, Kirkegaard K: Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol 2005, 3: e156. 10.1371/journal.pbio.0030156PubMedPubMedCentralCrossRef
66.
go back to reference Faivre S, Kroemer G, Raymond E: Current development of mTOR inhibitors as anticancer agents. Nat Rev Drug Discov 2006, 5: 671-688. 10.1038/nrd2062PubMedCrossRef Faivre S, Kroemer G, Raymond E: Current development of mTOR inhibitors as anticancer agents. Nat Rev Drug Discov 2006, 5: 671-688. 10.1038/nrd2062PubMedCrossRef
67.
go back to reference Sipula IJ, Brown NF, Perdomo G: Rapamycin-mediated inhibition of mammalian target of rapamycin in skeletal muscle cells reduces glucose utilization and increases fatty acid oxidation. Metabolism 2006, 55: 1637-1644. 10.1016/j.metabol.2006.08.002PubMedCrossRef Sipula IJ, Brown NF, Perdomo G: Rapamycin-mediated inhibition of mammalian target of rapamycin in skeletal muscle cells reduces glucose utilization and increases fatty acid oxidation. Metabolism 2006, 55: 1637-1644. 10.1016/j.metabol.2006.08.002PubMedCrossRef
68.
go back to reference Wei LH, Su H, Hildebrandt IJ, Phelps ME, Czernin J, Weber WA: Changes in tumor metabolism as readout for Mammalian target of rapamycin kinase inhibition by rapamycin in glioblastoma. Clin Cancer Res 2008, 14: 3416-3426. 10.1158/1078-0432.CCR-07-1824PubMedCrossRef Wei LH, Su H, Hildebrandt IJ, Phelps ME, Czernin J, Weber WA: Changes in tumor metabolism as readout for Mammalian target of rapamycin kinase inhibition by rapamycin in glioblastoma. Clin Cancer Res 2008, 14: 3416-3426. 10.1158/1078-0432.CCR-07-1824PubMedCrossRef
69.
go back to reference Edinger AL, Linardic CM, Chiang GG, Thompson CB, Abraham RT: Differential effects of rapamycin on mammalian target of rapamycin signaling functions in mammalian cells. Cancer Res 2003, 63: 8451-8460.PubMed Edinger AL, Linardic CM, Chiang GG, Thompson CB, Abraham RT: Differential effects of rapamycin on mammalian target of rapamycin signaling functions in mammalian cells. Cancer Res 2003, 63: 8451-8460.PubMed
70.
go back to reference Schieke SM, Phillips D, McCoy JP Jr, Aponte AM, Shen RF, Balaban RS, Finkel T: The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J Biol Chem 2006, 281: 27643-27652. 10.1074/jbc.M603536200PubMedCrossRef Schieke SM, Phillips D, McCoy JP Jr, Aponte AM, Shen RF, Balaban RS, Finkel T: The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J Biol Chem 2006, 281: 27643-27652. 10.1074/jbc.M603536200PubMedCrossRef
71.
go back to reference Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P: mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature 2007, 450: 736-740. 10.1038/nature06322PubMedCrossRef Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P: mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature 2007, 450: 736-740. 10.1038/nature06322PubMedCrossRef
72.
73.
go back to reference He S, Kato K, Jiang J, Wahl DR, Mineishi S, Fisher EM, Murasko DM, Glick GD, Zhang Y: Characterization of the metabolic phenotype of rapamycin-treated CD8+ T cells with augmented ability to generate long-lasting memory cells. PLoS One 2011, 6: e20107. 10.1371/journal.pone.0020107PubMedPubMedCentralCrossRef He S, Kato K, Jiang J, Wahl DR, Mineishi S, Fisher EM, Murasko DM, Glick GD, Zhang Y: Characterization of the metabolic phenotype of rapamycin-treated CD8+ T cells with augmented ability to generate long-lasting memory cells. PLoS One 2011, 6: e20107. 10.1371/journal.pone.0020107PubMedPubMedCentralCrossRef
74.
go back to reference Fang Y, Westbrook R, Hill C, Boparai RK, Arum O, Spong A, Wang F, Javors MA, Chen J, Sun LY, Bartke A: Duration of rapamycin treatment has differential effects on metabolism in mice. Cell Metab 2013, 17: 456-462. 10.1016/j.cmet.2013.02.008PubMedPubMedCentralCrossRef Fang Y, Westbrook R, Hill C, Boparai RK, Arum O, Spong A, Wang F, Javors MA, Chen J, Sun LY, Bartke A: Duration of rapamycin treatment has differential effects on metabolism in mice. Cell Metab 2013, 17: 456-462. 10.1016/j.cmet.2013.02.008PubMedPubMedCentralCrossRef
75.
go back to reference Bardell D: Glucose uptake and lactic acid production of adenovirus type 5-infected HEp-2 cells cultured under exponential growth and stationary phase conditions. Microbios 1977, 20: 139-144.PubMed Bardell D: Glucose uptake and lactic acid production of adenovirus type 5-infected HEp-2 cells cultured under exponential growth and stationary phase conditions. Microbios 1977, 20: 139-144.PubMed
76.
go back to reference Yu Y, Clippinger AJ, Alwine JC: Viral effects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection. Trends Microbiol 2011, 19: 360-367. 10.1016/j.tim.2011.04.002PubMedPubMedCentralCrossRef Yu Y, Clippinger AJ, Alwine JC: Viral effects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection. Trends Microbiol 2011, 19: 360-367. 10.1016/j.tim.2011.04.002PubMedPubMedCentralCrossRef
77.
go back to reference Munger J, Bajad SU, Coller HA, Shenk T, Rabinowitz JD: Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS Pathog 2006, 2: e132. 10.1371/journal.ppat.0020132PubMedPubMedCentralCrossRef Munger J, Bajad SU, Coller HA, Shenk T, Rabinowitz JD: Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS Pathog 2006, 2: e132. 10.1371/journal.ppat.0020132PubMedPubMedCentralCrossRef
78.
go back to reference Sehgal SN: Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem 1998, 31: 335-340. 10.1016/S0009-9120(98)00045-9PubMedCrossRef Sehgal SN: Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem 1998, 31: 335-340. 10.1016/S0009-9120(98)00045-9PubMedCrossRef
79.
go back to reference Grewe M, Gansauge F, Schmid RM, Adler G, Seufferlein T: Regulation of cell growth and cyclin D1 expression by the constitutively active FRAP-p70s6K pathway in human pancreatic cancer cells. Cancer Res 1999, 59: 3581-3587.PubMed Grewe M, Gansauge F, Schmid RM, Adler G, Seufferlein T: Regulation of cell growth and cyclin D1 expression by the constitutively active FRAP-p70s6K pathway in human pancreatic cancer cells. Cancer Res 1999, 59: 3581-3587.PubMed
80.
go back to reference Gaben AM, Saucier C, Bedin M, Barbu V, Mester J: Rapamycin inhibits cdk4 activation, p21(WAF1/CIP1) expression and G1-phase progression in transformed mouse fibroblasts. Int J Cancer 2004, 108: 200-206. 10.1002/ijc.11521PubMedCrossRef Gaben AM, Saucier C, Bedin M, Barbu V, Mester J: Rapamycin inhibits cdk4 activation, p21(WAF1/CIP1) expression and G1-phase progression in transformed mouse fibroblasts. Int J Cancer 2004, 108: 200-206. 10.1002/ijc.11521PubMedCrossRef
81.
go back to reference Kawamata S, Sakaida H, Hori T, Maeda M, Uchiyama T: The upregulation of p27Kip1 by rapamycin results in G1 arrest in exponentially growing T-cell lines. Blood 1998, 91: 561-569.PubMed Kawamata S, Sakaida H, Hori T, Maeda M, Uchiyama T: The upregulation of p27Kip1 by rapamycin results in G1 arrest in exponentially growing T-cell lines. Blood 1998, 91: 561-569.PubMed
Metadata
Title
Combination of autophagy inducer rapamycin and oncolytic adenovirus improves antitumor effect in cancer cells
Authors
Pei-Hsin Cheng
Serena Lian
Robin Zhao
Xiao-Mei Rao
Kelly M McMasters
Heshan Sam Zhou
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2013
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-10-293

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