Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Effects of hypoxia on human cancer cell line chemosensitivity

Authors: Sara Strese, Mårten Fryknäs, Rolf Larsson, Joachim Gullbo

Published in: BMC Cancer | Issue 1/2013

Login to get access

Abstract

Background

Environment inside even a small tumor is characterized by total (anoxia) or partial oxygen deprivation, (hypoxia). It has been shown that radiotherapy and some conventional chemotherapies may be less effective in hypoxia, and therefore it is important to investigate how different drugs act in different microenvironments. In this study we perform a large screening of the effects of 19 clinically used or experimental chemotherapeutic drugs on five different cell lines in conditions of normoxia, hypoxia and anoxia.

Methods

A panel of 19 commercially available drugs: 5-fluorouracil, acriflavine, bortezomib, cisplatin, digitoxin, digoxin, docetaxel, doxorubicin, etoposide, gemcitabine, irinotecan, melphalan, mitomycin c, rapamycin, sorafenib, thalidomide, tirapazamine, topotecan and vincristine were tested for cytotoxic activity on the cancer cell lines A2780 (ovarian), ACHN (renal), MCF-7 (breast), H69 (SCLC) and U-937 (lymphoma). Parallel aliquots of the cells were grown at different oxygen pressures and after 72 hours of drug exposure viability was measured with the fluorometric microculture cytotoxicity assay (FMCA).

Results

Sorafenib, irinotecan and docetaxel were in general more effective in an oxygenated environment, while cisplatin, mitomycin c and tirapazamine were more effective in a low oxygen environment. Surprisingly, hypoxia in H69 and MCF-7 cells mostly rendered higher drug sensitivity. In contrast ACHN appeared more sensitive to hypoxia, giving slower proliferating cells, and consequently, was more resistant to most drugs.

Conclusions

A panel of standard cytotoxic agents was tested against five different human cancer cell lines cultivated at normoxic, hypoxic and anoxic conditions. Results show that impaired chemosensitivity is not universal, in contrast different cell lines behave different and some drugs appear even less effective in normoxia than hypoxia.
Appendix
Available only for authorised users
Literature
1.
Durand RE, Raleigh JA: Identification of nonproliferating but viable hypoxic tumor cells in vivo. Cancer Res. 1998, 58 (16): 3547-3550.PubMed
2.
Evans SM, Joiner B, Jenkins WT, Laughlin KM, Lord EM, Koch CJ: Identification of hypoxia in cells and tissues of epigastric 9L rat glioma using EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide]. Br J Cancer. 1995, 72 (4): 875-882. 10.1038/bjc.1995.427.CrossRefPubMedPubMedCentral
3.
Partridge SE, Aquino-Parsons C, Luo C, Green A, Olive PL: A pilot study comparing intratumoral oxygenation using the comet assay following 2.5% and 5% carbogen and 100% oxygen. Int J Radiat Oncol Biol Phys. 2001, 49 (2): 575-580. 10.1016/S0360-3016(00)01504-2.CrossRefPubMed
4.
Tannock IF: The relation between cell proliferation and the vascular system in a transplanted mouse mammary tumour. Br J Cancer. 1968, 22 (2): 258-273. 10.1038/bjc.1968.34.CrossRefPubMedPubMedCentral
5.
Evans SM, Hahn SM, Magarelli DP, Koch CJ: Hypoxic heterogeneity in human tumors: EF5 binding, vasculature, necrosis, and proliferation. Am J Clin Oncol. 2001, 24 (5): 467-472. 10.1097/00000421-200110000-00011.CrossRefPubMed
6.
Hanahan D, Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996, 86 (3): 353-364. 10.1016/S0092-8674(00)80108-7.CrossRefPubMed
7.
Zetter BR: Angiogenesis and tumor metastasis. Annu Rev Med. 1998, 49: 407-424. 10.1146/annurev.med.49.1.407.CrossRefPubMed
8.
Brahimi-Horn MC, Chiche J, Pouyssegur J: Hypoxia and cancer. J Mol Med. 2007, 85 (12): 1301-1307. 10.1007/s00109-007-0281-3.CrossRefPubMed
9.
Hicklin DJ, Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005, 23 (5): 1011-1027.CrossRefPubMed
10.
Zhou J, Schmid T, Schnitzer S, Brune B: Tumor hypoxia and cancer progression. Cancer Lett. 2006, 237 (1): 10-21. 10.1016/j.canlet.2005.05.028.CrossRefPubMed
11.
Vander Heiden MG, Cantley LC, Thompson CB: Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009, 324 (5930): 1029-1033. 10.1126/science.1160809.CrossRefPubMedPubMedCentral
12.
Cardone RA, Casavola V, Reshkin SJ: The role of disturbed pH dynamics and the Na+/H + exchanger in metastasis. Nat Rev Cancer. 2005, 5 (10): 786-795. 10.1038/nrc1713.CrossRefPubMed
13.
Bogenrieder T, Herlyn M: Axis of evil: molecular mechanisms of cancer metastasis. Oncogene. 2003, 22 (42): 6524-6536. 10.1038/sj.onc.1206757.CrossRefPubMed
14.
Grau C, Khalil AA, Nordsmark M, Horsman MR, Overgaard J: The relationship between carbon monoxide breathing, tumour oxygenation and local tumour control in the C3H mammary carcinoma in vivo. Br J Cancer. 1994, 69 (1): 50-57. 10.1038/bjc.1994.8.CrossRefPubMedPubMedCentral
15.
Brizel DM, Dodge RK, Clough RW, Dewhirst MW: Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol. 1999, 53 (2): 113-117. 10.1016/S0167-8140(99)00102-4.CrossRefPubMed
16.
Hockel M, Schlenger K, Aral B, Mitze M, Schaffer U, Vaupel P: Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res. 1996, 56 (19): 4509-4515.PubMed
17.
Bodner G, Schocke MF, Rachbauer F, Seppi K, Peer S, Fierlinger A, Sununu T, Jaschke WR: Differentiation of malignant and benign musculoskeletal tumors: combined color and power Doppler US and spectral wave analysis. Radiology. 2002, 223 (2): 410-416. 10.1148/radiol.2232010406.CrossRefPubMed
18.
Brown JM, Giaccia AJ: The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res. 1998, 58 (7): 1408-1416.PubMed
19.
Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW, Giaccia AJ: Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature. 1996, 379 (6560): 88-91. 10.1038/379088a0.CrossRefPubMed
20.
Brown JM, Wilson WR: Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer. 2004, 4 (6): 437-447. 10.1038/nrc1367.CrossRefPubMed
21.
Roninson IB: The role of the MDR1 (P-glycoprotein) gene in multidrug resistance in vitro and in vivo. Biochem Pharmacol. 1992, 43 (1): 95-102. 10.1016/0006-2952(92)90666-7.CrossRefPubMed
22.
Wartenberg M, Ling FC, Muschen M, Klein F, Acker H, Gassmann M, Petrat K, Putz V, Hescheler J, Sauer H: Regulation of the multidrug resistance transporter P-glycoprotein in multicellular tumor spheroids by hypoxia-inducible factor (HIF-1) and reactive oxygen species. FASEB J. 2003, 17 (3): 503-505.PubMed
23.
Matzow T, Cowen RL, Williams KJ, Telfer BA, Flint PJ, Southgate TD, Saunders MP: Hypoxia-targeted over-expression of carboxylesterase as a means of increasing tumour sensitivity to irinotecan (CPT-11). J Gene Med. 2007, 9 (4): 244-252. 10.1002/jgm.1016.CrossRefPubMed
24.
Erler JT, Cawthorne CJ, Williams KJ, Koritzinsky M, Wouters BG, Wilson C, Miller C, Demonacos C, Stratford IJ, Dive C: Hypoxia-mediated down-regulation of Bid and Bax in tumors occurs via hypoxia-inducible factor 1-dependent and -independent mechanisms and contributes to drug resistance. Mol Cell Biol. 2004, 24 (7): 2875-2889. 10.1128/MCB.24.7.2875-2889.2004.CrossRefPubMedPubMedCentral
25.
Lash GE, Fitzpatrick TE, Graham CH: Effect of hypoxia on cellular adhesion to vitronectin and fibronectin. Biochem Biophys Res Commun. 2001, 287 (3): 622-629. 10.1006/bbrc.2001.5618.CrossRefPubMed
26.
Kim JY, Kim YJ, Lee S, Park JH: The critical role of ERK in death resistance and invasiveness of hypoxia-selected glioblastoma cells. BMC Cancer. 2009, 9: 27-10.1186/1471-2407-9-27.CrossRefPubMedPubMedCentral
27.
Carmeliet P, Dor Y, Herbert JM, Fukumura D, Brusselmans K, Dewerchin M, Neeman M, Bono F, Abramovitch R, Maxwell P, Koch CJ, Ratcliffe P, Moons L, Jain RK, Collen D, Keshert E: Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature. 1998, 394 (6692): 485-490. 10.1038/28867.CrossRefPubMed
28.
Griguer CE, Oliva CR, Kelley EE, Giles GI, Lancaster JR, Gillespie GY: Xanthine oxidase-dependent regulation of hypoxia-inducible factor in cancer cells. Cancer Res. 2006, 66 (4): 2257-2263. 10.1158/0008-5472.CAN-05-3364.CrossRefPubMed
29.
Baumann RP, Penketh PG, Seow HA, Shyam K, Sartorelli AC: Generation of oxygen deficiency in cell culture using a two-enzyme system to evaluate agents targeting hypoxic tumor cells. Radiat Res. 2008, 170 (5): 651-660. 10.1667/RR1431.1.CrossRefPubMedPubMedCentral
30.
Minchinton AI, Tannock IF: Drug penetration in solid tumours. Nat Rev Cancer. 2006, 6 (8): 583-592. 10.1038/nrc1893.CrossRefPubMed
31.
Karlsson H, Fryknas M, Larsson R, Nygren P: Loss of cancer drug activity in colon cancer HCT-116 cells during spheroid formation in a new 3-D spheroid cell culture system. Exp Cell Res. 2012, 318 (13): 1577-1585. 10.1016/j.yexcr.2012.03.026.CrossRefPubMed
32.
Hirschhaeuser F, Menne H, Dittfeld C, West J, Mueller-Klieser W, Kunz-Schughart LA: Multicellular tumor spheroids: an underestimated tool is catching up again. J Biotechnol. 2010, 148 (1): 3-15. 10.1016/j.jbiotec.2010.01.012.CrossRefPubMed
33.
Danielsen T, Skoyum R, Rofstad EK: Hypoxia-induced changes in radiation sensitivity in human melanoma cells: importance of oxygen-regulated proteins, adenylate energy charge and cell cycle distribution. Radiother Oncol. 1997, 44 (2): 177-182. 10.1016/S0167-8140(97)01929-4.CrossRefPubMed
34.
Yang SJ, Pyen J, Lee I, Lee H, Kim Y, Kim T: Cobalt chloride-induced apoptosis and extracellular signal-regulated protein kinase 1/2 activation in rat C6 glioma cells. J Biochem Mol Biol. 2004, 37 (4): 480-486. 10.5483/BMBRep.2004.37.4.480.CrossRefPubMed
35.
Koch S, Mayer F, Honecker F, Schittenhelm M, Bokemeyer C: Efficacy of cytotoxic agents used in the treatment of testicular germ cell tumours under normoxic and hypoxic conditions in vitro. Br J Cancer. 2003, 89 (11): 2133-2139. 10.1038/sj.bjc.6601375.CrossRefPubMedPubMedCentral
36.
Hay MP, Gamage SA, Kovacs MS, Pruijn FB, Anderson RF, Patterson AV, Wilson WR, Brown JM, Denny WA: Structure-activity relationships of 1,2,4-benzotriazine 1,4-dioxides as hypoxia-selective analogues of tirapazamine. J Med Chem. 2003, 46 (1): 169-182. 10.1021/jm020367+.CrossRefPubMed
37.
Sakata K, Kwok TT, Murphy BJ, Laderoute KR, Gordon GR, Sutherland RM: Hypoxia-induced drug resistance: comparison to P-glycoprotein-associated drug resistance. Br J Cancer. 1991, 64 (5): 809-814. 10.1038/bjc.1991.405.CrossRefPubMedPubMedCentral
38.
Rohwer N, Dame C, Haugstetter A, Wiedenmann B, Detjen K, Schmitt CA, Cramer T: Hypoxia-inducible factor 1alpha determines gastric cancer chemosensitivity via modulation of p53 and NF-kappaB. PLoS One. 2010, 5 (8): e12038-10.1371/journal.pone.0012038.CrossRefPubMedPubMedCentral
39.
Lee K, Zhang H, Qian DZ, Rey S, Liu JO, Semenza GL: Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proc Natl Acad Sci USA. 2009, 106 (42): 17910-17915. 10.1073/pnas.0909353106.CrossRefPubMedPubMedCentral
40.
Roccaro AM, Hideshima T, Raje N, Kumar S, Ishitsuka K, Yasui H, Shiraishi N, Ribatti D, Nico B, Vacca A, Dammacco F, Richardson PG, Anderson KC: Bortezomib mediates antiangiogenesis in multiple myeloma via direct and indirect effects on endothelial cells. Cancer Res. 2006, 66 (1): 184-191. 10.1158/0008-5472.CAN-05-1195.CrossRefPubMed
41.
Shin DH, Chun YS, Lee DS, Huang LE, Park JW: Bortezomib inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated repression of hypoxia-inducible factor-1. Blood. 2008, 111 (6): 3131-3136. 10.1182/blood-2007-11-120576.CrossRefPubMed
42.
Duyndam MC, van Berkel MP, Dorsman JC, Rockx DA, Pinedo HM, Boven E: Cisplatin and doxorubicin repress Vascular Endothelial Growth Factor expression and differentially down-regulate Hypoxia-inducible Factor I activity in human ovarian cancer cells. Biochem Pharmacol. 2007, 74 (2): 191-201. 10.1016/j.bcp.2007.04.003.CrossRefPubMed
43.
Zhang H, Qian DZ, Tan YS, Lee K, Gao P, Ren YR, Rey S, Hammers H, Chang D, Pili R, Dang CV, Liu JO, Semenza GL: Digoxin and other cardiac glycosides inhibit HIF-1alpha synthesis and block tumor growth. Proc Natl Acad Sci USA. 2008, 105 (50): 19579-19586. 10.1073/pnas.0809763105.CrossRefPubMedPubMedCentral
44.
Escuin D, Kline ER, Giannakakou P: Both microtubule-stabilizing and microtubule-destabilizing drugs inhibit hypoxia-inducible factor-1alpha accumulation and activity by disrupting microtubule function. Cancer Res. 2005, 65 (19): 9021-9028. 10.1158/0008-5472.CAN-04-4095.CrossRefPubMed
45.
Forde JC, Perry AS, Brennan K, Martin LM, Lawler MP, Lynch TH, Hollywood D, Marignol L: Docetaxel maintains its cytotoxic activity under hypoxic conditions in prostate cancer cells. Urol Oncol. 2010, 30: 912-919.CrossRefPubMed
46.
Kennedy KA, Siegfried JM, Sartorelli AC, Tritton TR: Effects of anthracyclines on oxygenated and hypoxic tumor cells. Cancer Res. 1983, 43 (1): 54-59.PubMed
47.
Sermeus A, Cosse JP, Crespin M, Mainfroid V, de Longueville F, Ninane N, Raes M, Remacle J, Michiels C: Hypoxia induces protection against etoposide-induced apoptosis: molecular profiling of changes in gene expression and transcription factor activity. Mol Cancer. 2008, 7: 27-CrossRefPubMedPubMedCentral
48.
Sullivan R, Graham CH: Hypoxia prevents etoposide-induced DNA damage in cancer cells through a mechanism involving hypoxia-inducible factor 1. Mol Cancer Ther. 2009, 8 (6): 1702-1713. 10.1158/1535-7163.MCT-08-1090.CrossRefPubMed
49.
Onozuka H, Tsuchihara K, Esumi H: Hypoglycemic/hypoxic condition in vitro mimicking the tumor microenvironment markedly reduced the efficacy of anticancer drugs. Cancer Sci. 2011, 102 (5): 975-982. 10.1111/j.1349-7006.2011.01880.x.CrossRefPubMed
50.
Kasuya K, Tsuchida A, Nagakawa Y, Suzuki M, Abe Y, Itoi T, Serizawa H, Nagao T, Shimazu M, Aoki T: Hypoxia-inducible factor-1alpha expression and gemcitabine chemotherapy for pancreatic cancer. Oncol Rep. 2011, 26 (6): 1399-1406.PubMed
51.
Kamiyama H, Takano S, Tsuboi K, Matsumura A: Anti-angiogenic effects of SN38 (active metabolite of irinotecan): inhibition of hypoxia-inducible factor 1 alpha (HIF-1alpha)/vascular endothelial growth factor (VEGF) expression of glioma and growth of endothelial cells. J Cancer Res Clin Oncol. 2005, 131 (4): 205-213. 10.1007/s00432-004-0642-z.CrossRefPubMed
52.
de Wilt JH, Manusama ER, van Tiel ST, van Ijken MG, ten Hagen TL, Eggermont AM: Prerequisites for effective isolated limb perfusion using tumour necrosis factor alpha and melphalan in rats. Br J Cancer. 1999, 80 (1–2): 161-166.CrossRefPubMed
53.
Hu Y, Kirito K, Yoshida K, Mitsumori T, Nakajima K, Nozaki Y, Hamanaka S, Nagashima T, Kunitama M, Sakoe K, Komatsu N: Inhibition of hypoxia-inducible factor-1 function enhances the sensitivity of multiple myeloma cells to melphalan. Mol Cancer Ther. 2009, 8 (8): 2329-2338. 10.1158/1535-7163.MCT-09-0150.CrossRefPubMed
54.
Teicher BA, Lazo JS, Sartorelli AC: Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells. Cancer Res. 1981, 41 (1): 73-81.PubMed
55.
Hudson CC, Liu M, Chiang GG, Otterness DM, Loomis DC, Kaper F, Giaccia AJ, Abraham RT: Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol Cell Biol. 2002, 22 (20): 7004-7014. 10.1128/MCB.22.20.7004-7014.2002.CrossRefPubMedPubMedCentral
56.
Mayerhofer M, Valent P, Sperr WR, Griffin JD, Sillaber C: BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor-1alpha, through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin. Blood. 2002, 100 (10): 3767-3775. 10.1182/blood-2002-01-0109.CrossRefPubMed
57.
Pencreach E, Guerin E, Nicolet C, Lelong-Rebel I, Voegeli AC, Oudet P, Larsen AK, Gaub MP, Guenot D: Marked activity of irinotecan and rapamycin combination toward colon cancer cells in vivo and in vitro is mediated through cooperative modulation of the mammalian target of rapamycin/hypoxia-inducible factor-1alpha axis. Clin Cancer Res. 2009, 15 (4): 1297-1307. 10.1158/1078-0432.CCR-08-0889.CrossRefPubMed
58.
Liu L, Cao Y, Chen C, Zhang X, McNabola A, Wilkie D, Wilhelm S, Lynch M, Carter C: Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006, 66 (24): 11851-11858. 10.1158/0008-5472.CAN-06-1377.CrossRefPubMed
59.
D’Amato RJ, Loughnan MS, Flynn E, Folkman J: Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA. 1994, 91 (9): 4082-4085. 10.1073/pnas.91.9.4082.CrossRefPubMedPubMedCentral
60.
Bauer KS, Dixon SC, Figg WD: Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent. Biochem Pharmacol. 1998, 55 (11): 1827-1834. 10.1016/S0006-2952(98)00046-X.CrossRefPubMed
61.
Brown JM: The hypoxic cell: a target for selective cancer therapy–eighteenth Bruce F Cain Memorial Award lecture. Cancer Res. 1999, 59 (23): 5863-5870.PubMed
62.
Marcu L, Olver I: Tirapazamine: from bench to clinical trials. Curr Clin Pharmacol. 2006, 1 (1): 71-79. 10.2174/157488406775268192.CrossRefPubMed
63.
Reddy SB, Williamson SK: Tirapazamine: a novel agent targeting hypoxic tumor cells. Expert Opin Investig Drugs. 2009, 18 (1): 77-87. 10.1517/13543780802567250.CrossRefPubMed
64.
Rapisarda A, Uranchimeg B, Scudiero DA, Selby M, Sausville EA, Shoemaker RH, Melillo G: Identification of small molecule inhibitors of hypoxia-inducible factor 1 transcriptional activation pathway. Cancer Res. 2002, 62 (15): 4316-4324.PubMed
65.
Kummar S, Raffeld M, Juwara L, Horneffer Y, Strassberger A, Allen D, Steinberg SM, Rapisarda A, Spencer SD, Figg WD, Chen X, Turkbey IB, Choyke P, Murgo AJ, Doroshow JH, Melillo G: Multihistology, target-driven pilot trial of oral topotecan as an inhibitor of hypoxia-inducible factor-1alpha in advanced solid tumors. Clin Cancer Res. 2011, 17 (15): 5123-5131. 10.1158/1078-0432.CCR-11-0682.CrossRefPubMedPubMedCentral
66.
Liu L, Ning X, Sun L, Zhang H, Shi Y, Guo C, Han S, Liu J, Sun S, Han Z, Wu K, Fan D: Hypoxia-inducible factor-1 alpha contributes to hypoxia-induced chemoresistance in gastric cancer. Cancer Sci. 2008, 99 (1): 121-128.PubMed
67.
Lindhagen E, Nygren P, Larsson R: The fluorometric microculture cytotoxicity assay. Nat Protoc. 2008, 3 (8): 1364-1369. 10.1038/nprot.2008.114.CrossRefPubMed
68.
Larsson R, Kristensen J, Sandberg C, Nygren P: Laboratory determination of chemotherapeutic drug resistance in tumor cells from patients with leukemia, using a fluorometric microculture cytotoxicity assay (FMCA). Int J Cancer. 1992, 50 (2): 177-185. 10.1002/ijc.2910500204.CrossRefPubMed
69.
Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, Lerner J, Brunet JP, Subramanian A, Ross KN, Reich M, Hieronymus H, Wei G, Armstrong SA, Haggarty SJ, Clemons PA, Wei R, Carr SA, Lander ES, Golub TR: The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006, 313 (5795): 1929-1935. 10.1126/science.1132939.CrossRefPubMed
70.
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP: Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005, 102 (43): 15545-15550. 10.1073/pnas.0506580102.CrossRefPubMedPubMedCentral
71.
da Huang W, Sherman BT, Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009, 4 (1): 44-57.CrossRefPubMed
72.
Elvidge GP, Glenny L, Appelhoff RJ, Ratcliffe PJ, Ragoussis J, Gleadle JM: Concordant regulation of gene expression by hypoxia and 2-oxoglutarate-dependent dioxygenase inhibition: the role of HIF-1alpha, HIF-2alpha, and other pathways. J Biol Chem. 2006, 281 (22): 15215-15226. 10.1074/jbc.M511408200.CrossRefPubMed
73.
Vaupel P, Thews O, Hoeckel M: Treatment resistance of solid tumors: role of hypoxia and anemia. Med Oncol. 2001, 18 (4): 243-259. 10.1385/MO:18:4:243.CrossRefPubMed
74.
Rohwer N, Cramer T: Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways. Drug Resist Updat. 2011, 14 (3): 191-201. 10.1016/j.drup.2011.03.001.CrossRefPubMed
75.
Schwartz HS: Pharmacology of mitomycin C. III. In vitro metabolism by rat liver. J Pharmacol Exp Ther. 1962, 136: 250-258.PubMed
76.
Iwai A, Fujii Y, Kawakami S, Takazawa R, Kageyama Y, Yoshida MA, Kihara K: Down-regulation of vascular endothelial growth factor in renal cell carcinoma cells by glucocorticoids. Mol Cell Endocrinol. 2004, 226 (1–2): 11-17.CrossRefPubMed
77.
Tochizawa S, Masumori N, Yanai Y, Ohmoto Y, Yabuuchi Y, Tsukamoto T: Antitumor effects of a combination of interferon-alpha and sorafenib on human renal carcinoma cell lines. Biomed Res. 2008, 29 (6): 271-278. 10.2220/biomedres.29.271.CrossRefPubMed
78.
Lee TH, Seng S, Sekine M, Hinton C, Fu Y, Avraham HK, Avraham S: Vascular endothelial growth factor mediates intracrine survival in human breast carcinoma cells through internally expressed VEGFR1/FLT1. PLoS Med. 2007, 4 (6): e186-10.1371/journal.pmed.0040186.CrossRefPubMedPubMedCentral
79.
Lee JH, Shim JW, Choi YJ, Heo K, Yang K: The combination of sorafenib and radiation preferentially inhibits breast cancer stem cells by suppressing HIF-1alpha expression. Oncol Rep. 2013, 29 (3): 917-924.PubMedPubMedCentral
80.
Spannuth WA, Nick AM, Jennings NB, Armaiz-Pena GN, Mangala LS, Danes CG, Lin YG, Merritt WM, Thaker PH, Kamat AA, Han LY, Tonra JR, Coleman RL, Ellis LM, Sood AK: Functional significance of VEGFR-2 on ovarian cancer cells. Int J Cancer. 2009, 124 (5): 1045-1053. 10.1002/ijc.24028.CrossRefPubMedPubMedCentral
Metadata
Title
Effects of hypoxia on human cancer cell line chemosensitivity
Authors
Sara Strese
Mårten Fryknäs
Rolf Larsson
Joachim Gullbo
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-331

Other articles of this Issue 1/2013

BMC Cancer 1/2013 Go to the issue

Research article

Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival

Research article

Prognostic impact of serum CYFRA 21–1 in patients with advanced lung adenocarcinoma: a retrospective study

Research article

Prediction of metachronous multiple primary cancers following the curative resection of gastric cancer

Technical advance

Simultaneous identification of 36 mutations in KRAS codons 61and 146, BRAF, NRAS, and PIK3CAin a single reaction by multiplex assay kit

Research article

Elevated cyclin B2 expression in invasive breast carcinoma is associated with unfavorable clinical outcome

Research article

NK-cell-dependent killing of colon carcinoma cells is mediated by natural cytotoxicity receptors (NCRs) and stimulated by parvovirus infection of target cells
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits