Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Sep 21, 2008; 14(35): 5403-5411
Published online Sep 21, 2008. doi: 10.3748/wjg.14.5403
Anti-tumor activity of erlotinib in the BxPC-3 pancreatic cancer cell line
Ying-Ying Lu, Da-Dao Jing, Ming Xu, Kai Wu, Xing-Peng Wang
Ying-Ying Lu, Da-Dao Jing, Kai Wu, Xing-Peng Wang, Department of Gastroenterology, Affiliated First People’s Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
Ming Xu, Department of Gastroenterology, Wuxi Second People’s Hospital, Wuxi 214002, Jiangsu Province, China
Author contributions: Lu YY and Jing DD contributed equally to this work; Jing DD and Wang XP designed the research; Lu YY, Xu M and Wu K performed the research; Lu YY analyzed the data and wrote the paper.
Correspondence to: Dr. Da-Dao Jing, Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiao Tong University, 100 Haining RD, Hongkou District, Shanghai 200080, China.
Telephone: +86-21-63240090-3141 Fax: +86-21-66302029
Received: April 26, 2008
Revised: June 23, 2008
Accepted: June 30, 2008
Published online: September 21, 2008

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 endothelial cell growth factor (VEGF) were measured with 3-(4,5-dimethylthiazole-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 G1 arrest and induced cell apoptosis, and suppressed capillary formation of endothelium in vitro. Expressions of VEGF were significantly down-regulated at a high concentration of 200 μmol/L, however, the expressions of bcl-2 and bcl-xl were decreased at 50 μmol/L. In vivo, Erlotinib-treated mice demon-strated 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.

Keywords: Pancreatic cancer, Erlotinib, Epidermal growth factor receptor, Human xenograft model, Angiogenesis