Skip to main content
Top
Published in: Tumor Biology 1/2012

01-02-2012 | Research Article

Lentivirus-delivered Krüppel-like factor 8 small interfering RNA inhibits gastric cancer cell growth in vitro and in vivo

Authors: Lili Liu, Na Liu, Min Xu, Yi Liu, Jie Min, Hailin Pang, Ning Zhang, Hongbo Zhang, Helong Zhang

Published in: Tumor Biology | Issue 1/2012

Login to get access

Abstract

We found that the transcription factor Krüppel-like factor 8 (KLF8) was highly expressed in gastric cancer tissues and cell lines compared with adjacent noncancerous regions and gastric epithelial mucosa cells. We employed a lentivirus-mediated RNAi technique to knockdown KLF8 expression in gastric cancer cell line SGC7901 and observed its effects on cell growth in vitro and in vivo. Knockdown of KLF8 inhibited SGC7901 cell proliferation, promoted cell apoptosis, inhibited the tumorigenicity of SGC7901 cells, and significantly decreased tumor growth when the cells were injected into nude mice. These results indicated that overexpression of KLF8 may influence the biological behavior of SGC7901 gastric cancer cells. Knockdown of KLF8 expression by lentivirus-delivered siRNA may be useful as a therapeutic agent for the treatment of gastric cancer.
Literature
1.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.PubMedCrossRef Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.PubMedCrossRef
2.
go back to reference Sasako M, Inoue M, Lin JT, Khor C, Yang HK, Ohtsu A. Gastric Cancer Working Group report. Jpn J Clin Oncol. 2010;40 Suppl 1:i28–37.PubMedCrossRef Sasako M, Inoue M, Lin JT, Khor C, Yang HK, Ohtsu A. Gastric Cancer Working Group report. Jpn J Clin Oncol. 2010;40 Suppl 1:i28–37.PubMedCrossRef
3.
go back to reference Lim L, Michael M, Mann GB, Leong T. Adjuvant therapy in gastric cancer. J Clin Oncol. 2005;23:6220–32.PubMedCrossRef Lim L, Michael M, Mann GB, Leong T. Adjuvant therapy in gastric cancer. J Clin Oncol. 2005;23:6220–32.PubMedCrossRef
4.
go back to reference Stein HJ, Sendler A, Fink U, Siewert JR. Multidisciplinary approach to esophageal and gastric cancer. Surg Clin North Am. 2000;80:659–82. discussions 683–656.PubMedCrossRef Stein HJ, Sendler A, Fink U, Siewert JR. Multidisciplinary approach to esophageal and gastric cancer. Surg Clin North Am. 2000;80:659–82. discussions 683–656.PubMedCrossRef
5.
go back to reference Pearson R, Fleetwood J, Eaton S, Crossley M, Bao S. Kruppel-like transcription factors: a functional family. Int J Biochem Cell Biol. 2008;40:1996–2001.PubMedCrossRef Pearson R, Fleetwood J, Eaton S, Crossley M, Bao S. Kruppel-like transcription factors: a functional family. Int J Biochem Cell Biol. 2008;40:1996–2001.PubMedCrossRef
6.
go back to reference Wang X, Zheng M, Liu G, Xia W, McKeown-Longo PJ, Hung MC, et al. Kruppel-like factor 8 induces epithelial to mesenchymal transition and epithelial cell invasion. Cancer Res. 2007;67:7184–93.PubMedCrossRef Wang X, Zheng M, Liu G, Xia W, McKeown-Longo PJ, Hung MC, et al. Kruppel-like factor 8 induces epithelial to mesenchymal transition and epithelial cell invasion. Cancer Res. 2007;67:7184–93.PubMedCrossRef
7.
go back to reference Wang X, Zhao J. KLF8 transcription factor participates in oncogenic transformation. Oncogene. 2007;26:456–61.PubMedCrossRef Wang X, Zhao J. KLF8 transcription factor participates in oncogenic transformation. Oncogene. 2007;26:456–61.PubMedCrossRef
8.
go back to reference Wang X, Urvalek AM, Liu J, Zhao J. Activation of KLF8 transcription by focal adhesion kinase in human ovarian epithelial and cancer cells. J Biol Chem. 2008;283:13934–13942. Wang X, Urvalek AM, Liu J, Zhao J. Activation of KLF8 transcription by focal adhesion kinase in human ovarian epithelial and cancer cells. J Biol Chem. 2008;283:13934–13942.
9.
go back to reference Wang X, Lu H, Urvalek AM, Li T, Yu L, Lamar J, et al. KLF8 promotes human breast cancer cell invasion and metastasis by transcriptional activation of MMP9. Oncogene. 2011;30:1901–11.PubMedCrossRef Wang X, Lu H, Urvalek AM, Li T, Yu L, Lamar J, et al. KLF8 promotes human breast cancer cell invasion and metastasis by transcriptional activation of MMP9. Oncogene. 2011;30:1901–11.PubMedCrossRef
10.
go back to reference Fu WJ, Li JC, Wu XY, Yang ZB, Mo ZN, Huang JW, et al. Small interference RNA targeting Kruppel-like factor 8 inhibits the renal carcinoma 786–0 cells growth in vitro and in vivo. J Cancer Res Clin Oncol. 2010;136:1255–65.PubMedCrossRef Fu WJ, Li JC, Wu XY, Yang ZB, Mo ZN, Huang JW, et al. Small interference RNA targeting Kruppel-like factor 8 inhibits the renal carcinoma 786–0 cells growth in vitro and in vivo. J Cancer Res Clin Oncol. 2010;136:1255–65.PubMedCrossRef
11.
go back to reference Lois C, Hong EJ, Pease S, Brown EJ, Baltimore D. Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science. 2002;295:868–72.PubMedCrossRef Lois C, Hong EJ, Pease S, Brown EJ, Baltimore D. Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science. 2002;295:868–72.PubMedCrossRef
12.
go back to reference Milner AE, Levens JM, Gregory CD. Flow cytometric methods of analyzing apoptotic cells. Methods Mol Biol. 1998;80:347–54.PubMedCrossRef Milner AE, Levens JM, Gregory CD. Flow cytometric methods of analyzing apoptotic cells. Methods Mol Biol. 1998;80:347–54.PubMedCrossRef
13.
go back to reference Liu N, Bi F, Pan Y, Sun L, Xue Y, Shi Y, et al. Reversal of the malignant phenotype of gastric cancer cells by inhibition of RhoA expression and activity. Clin Cancer Res. 2004;10:6239–47.PubMedCrossRef Liu N, Bi F, Pan Y, Sun L, Xue Y, Shi Y, et al. Reversal of the malignant phenotype of gastric cancer cells by inhibition of RhoA expression and activity. Clin Cancer Res. 2004;10:6239–47.PubMedCrossRef
14.
go back to reference Guinn BA, Mulherkar R. International progress in cancer gene therapy. Cancer Gene Ther. 2008;15:765–75.PubMedCrossRef Guinn BA, Mulherkar R. International progress in cancer gene therapy. Cancer Gene Ther. 2008;15:765–75.PubMedCrossRef
15.
go back to reference Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer. 2005;5:845–56.PubMedCrossRef Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer. 2005;5:845–56.PubMedCrossRef
17.
go back to reference Fuchs BC, Fujii T, Dorfman JD, Goodwin JM, Zhu AX, Lanuti M, et al. Epithelial-to-mesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells. Cancer Res. 2008;68:2391–9.PubMedCrossRef Fuchs BC, Fujii T, Dorfman JD, Goodwin JM, Zhu AX, Lanuti M, et al. Epithelial-to-mesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells. Cancer Res. 2008;68:2391–9.PubMedCrossRef
18.
go back to reference McLean GW, Komiyama NH, Serrels B, Asano H, Reynolds L, Conti F, et al. Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression. Genes Dev. 2004;18:2998–3003.PubMedCrossRef McLean GW, Komiyama NH, Serrels B, Asano H, Reynolds L, Conti F, et al. Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression. Genes Dev. 2004;18:2998–3003.PubMedCrossRef
19.
go back to reference Mitra SK, Lim ST, Chi A, Schlaepfer DD. Intrinsic focal adhesion kinase activity controls orthotopic breast carcinoma metastasis via the regulation of urokinase plasminogen activator expression in a syngeneic tumor model. Oncogene. 2006;25:4429–40.PubMedCrossRef Mitra SK, Lim ST, Chi A, Schlaepfer DD. Intrinsic focal adhesion kinase activity controls orthotopic breast carcinoma metastasis via the regulation of urokinase plasminogen activator expression in a syngeneic tumor model. Oncogene. 2006;25:4429–40.PubMedCrossRef
20.
go back to reference Zhao J, Bian ZC, Yee K, Chen BP, Chien S, Guan JL. Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression. Mol Cell. 2003;11:1503–15.PubMedCrossRef Zhao J, Bian ZC, Yee K, Chen BP, Chien S, Guan JL. Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression. Mol Cell. 2003;11:1503–15.PubMedCrossRef
21.
go back to reference Liu L, Ning X, Sun L, Zhang H, Shi Y, Guo C, et al. Hypoxia-inducible factor-1 alpha contributes to hypoxia-induced chemoresistance in gastric cancer. Cancer Sci. 2008;99:121–8.PubMed Liu L, Ning X, Sun L, Zhang H, Shi Y, Guo C, et al. Hypoxia-inducible factor-1 alpha contributes to hypoxia-induced chemoresistance in gastric cancer. Cancer Sci. 2008;99:121–8.PubMed
Metadata
Title
Lentivirus-delivered Krüppel-like factor 8 small interfering RNA inhibits gastric cancer cell growth in vitro and in vivo
Authors
Lili Liu
Na Liu
Min Xu
Yi Liu
Jie Min
Hailin Pang
Ning Zhang
Hongbo Zhang
Helong Zhang
Publication date
01-02-2012
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 1/2012
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-011-0245-7

Other articles of this Issue 1/2012

Tumor Biology 1/2012 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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