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.
Similar content being viewed by others
References
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.
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.
Lim L, Michael M, Mann GB, Leong T. Adjuvant therapy in gastric cancer. J Clin Oncol. 2005;23:6220–32.
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.
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.
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.
Wang X, Zhao J. KLF8 transcription factor participates in oncogenic transformation. Oncogene. 2007;26:456–61.
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, 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.
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.
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.
Milner AE, Levens JM, Gregory CD. Flow cytometric methods of analyzing apoptotic cells. Methods Mol Biol. 1998;80:347–54.
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.
Guinn BA, Mulherkar R. International progress in cancer gene therapy. Cancer Gene Ther. 2008;15:765–75.
Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer. 2005;5:845–56.
Lever AM, Strappe PM, Zhao J. Lentiviral vectors. J Biomed Sci. 2004;11:439–49.
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.
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.
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.
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.
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.
Acknowledgement
This work was supported by the National Foundation of Natural Sciences, China (Number: 30971338).
Conflicts of interest
None.
Author information
Authors and Affiliations
Corresponding authors
Additional information
Lili Liu and Na Liu contributed equally to this work.
Rights and permissions
About this article
Cite this article
Liu, L., Liu, N., Xu, M. et al. Lentivirus-delivered Krüppel-like factor 8 small interfering RNA inhibits gastric cancer cell growth in vitro and in vivo. Tumor Biol. 33, 53–61 (2012). https://doi.org/10.1007/s13277-011-0245-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-011-0245-7