rAd-p53 增强人胃癌细胞对化疗的敏感性。
rAd-p53 enhances the sensitivity of human gastric cancer cells to chemotherapy.
机构信息
Department of Gastroenterology, First People's Hospital of Xuzhou, Xuzhou 221002, Jiangsu Province, China.
出版信息
World J Gastroenterol. 2011 Oct 14;17(38):4289-97. doi: 10.3748/wjg.v17.i38.4289.
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.
目的
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。
方法
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。
结果
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。
结论
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。
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