Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 14, 2011; 17(38): 4289-4297
Published online Oct 14, 2011. doi: 10.3748/wjg.v17.i38.4289
rAd-p53 enhances the sensitivity of human gastric cancer cells to chemotherapy
Guang-Xia Chen, Li-Hong Zheng, Shi-Yu Liu, Xiao-Hua He
Guang-Xia Chen, Shi-Yu Liu, Xiao-Hua He, Department of Gastroenterology, First People’s Hospital of Xuzhou, Xuzhou 221002, Jiangsu Province, China
Li-Hong Zheng, Yantai Economic and Technological Development Zone Hospital, Yantai 264006, Shandong Province, China
Author contributions: Chen GX, Zheng LH, Liu SY and He XH conducted the experiments; Chen GX wrote the manuscript.
Supported by Xuzhou Science and Technology Development Fund, No. XM07C039
Correspondence to: Dr. Guang-Xia Chen, Department of Gastroenterology, First People’s Hospital of Xuzhou, Xuzhou 221002, Jiangsu Province, China. gx_chen2008@yahoo.cn
Telephone: +86-516-85803186 Fax: +86-516-85803011
Received: December 19, 2010
Revised: April 19, 2011
Accepted: April 26, 2011
Published online: October 14, 2011
Abstract

AIM: To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy.

METHODS: Three gastric cancer cell lines with distinct levels of differentiation were treated with various doses of rAd-p53 alone, oxaliplatin (OXA) alone, or a combination of both. Cell growth was assessed with an 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide assay and the expression levels of p53, Bax and Bcl-2 were determined by immunohistochemistry. The presence of apoptosis and the expression of caspase-3 were determined using flow cytometry.

RESULTS: Treatment with rAd-p53 or OXA alone inhibited gastric cancer cell growth in a time- and dose-dependent manner; moreover, significant synergistic effects were observed when these treatments were combined. Immunohistochemical analysis demonstrated that treatment with rAd-p53 alone, OXA alone or combined treatment led to decreased Bcl-2 expression and increased Bax expression in gastric cancer cells. Furthermore, flow cytometry showed that rAd-p53 alone, OXA alone or combination treatment induced apoptosis of gastric cancer cells, which was accompanied by increased expression of caspase-3.

CONCLUSION: rAd-p53 enhances the sensitivity of gastric cancer cells to chemotherapy by promoting apoptosis. Thus, our results suggest that p53 gene therapy combined with chemotherapy represents a novel avenue for gastric cancer treatment.

Keywords: Gastric cancer; rAd-p53; Oxaliplatin; Chemosensitivity; Apoptosis