Department of Gastroenterology, First People's Hospital of Xuzhou, Xuzhou 221002, Jiangsu Province, China.
World J Gastroenterol. 2011 Oct 14;17(38):4289-97. doi: 10.3748/wjg.v17.i38.4289.
To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy.
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.
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.
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.
通过确定重组人腺病毒-53（rAd-p53）是否增强胃癌细胞对化疗的敏感性来研究其潜在的抗肿瘤作用。
用不同剂量的 rAd-p53、奥沙利铂（OXA）或两者联合处理三种分化程度不同的胃癌细胞系。用 3-(4,5)-二甲基噻唑(-z-y1)-3,5-二苯基四氮唑溴盐比色法评估细胞生长情况，并用免疫组织化学法测定 p53、Bax 和 Bcl-2 的表达水平。用流式细胞术检测凋亡的存在和 caspase-3 的表达。
rAd-p53 或 OXA 单独处理可呈时间和剂量依赖性抑制胃癌细胞生长；此外，这些处理联合时观察到显著的协同作用。免疫组织化学分析表明，rAd-p53 单独、OXA 单独或联合处理可降低胃癌细胞中 Bcl-2 的表达并增加 Bax 的表达。此外，流式细胞术显示 rAd-p53 单独、OXA 单独或联合处理可诱导胃癌细胞凋亡，并伴有 caspase-3 的表达增加。
rAd-p53 通过促进细胞凋亡增强胃癌细胞对化疗的敏感性。因此，我们的结果表明 p53 基因治疗联合化疗为胃癌治疗提供了新途径。
