科研之友
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摘要
AIM: To investigate the effect and mechanism of action of erlotinib, an epidermal growth factor receptor (EGFR) small molecule tyrosine kinase inhibitor (TKI), in the human pancreatic cancer cell line BxPC-3 both in vitro and in vivo. @@@ METHODS: In vitro, human pancreatic cancer cell line BxPC-3 was exposed to varying concentrations of erlotinib, and its effects on proliferation, cell cycle distribution, apoptosis and the expression of pro-and antiapoptotic factors such as bcl-2, bcl-xl, bax and bak, and the expression of vascular enclothelial cell growth factor (VEGF) were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis, terminal deoxynucleotidyl transferase-mediated nick end labeling assay (TUNEL), and reverse transcription-polymerase chain reaction (RT-PCR). Potential effect of erlotinib on angiogenesis was examined by tube formation assay. Tumor growth suppression was observed in xenografted nude mice with pancreatic cancer in vivo. Immunohistochemical (IHC) staining for EGFR and factor VIII-related antigen was undertaken to detect the microvessel density and VEGF expression in tumor tissue in xenograft nude mice. @@@ RESULTS: Erlotinib, as a single agent, repressed BxPC-3 cell growth in a dose-dependent manner, triggered G, arrest and induced cell apoptosis, and suppressed capillary formation of enclothelium in vitro. Expressions of VEGF were significantly down-regulated at a high concentration of 200 mu mol/L, however, the expressions of bcl-2 and bcl-xl were decreased at 50 mu mol/L. In vivo, Erlotinib-treated mice demonstrated a reduced tumor volume, weight and microvessel density as compared to the control. IHC staining showed decreased expression of EGFR and RT-PCR had lower VEGF expression in treated mice. @@@ CONCLUSION: The in vitro and in vivo findings provide evidence that BxPC-3 cells are inhibited with erlotinib treatment. Inhibition of EGFR may be a promising adjuvant chemotherapy strategy in pancreatic cancer treatment.
- 出版日期2008-9-21
- 单位上海交通大学
