中效原理在胃癌联合化疗中的应用及药物抗癌机制的初步探索

目的 运用中效原理分析姜黄素联合顺铂或塞来昔布对胃癌SGC-7901细胞的化疗效应,并初步探索上述三种药物对胃癌的抗癌机制.方法 将实验组分为姜黄素组、顺铂组、塞来昔布组、姜黄素联合顺铂组、姜黄素联合塞来昔布组,用相应药物作用于胃癌SGC-7901细胞,阴性对照组为不含药物组.然后采用MTT法测定药物对SGC-7901细胞的增殖抑制率,并运用中效原理分析药物联用的效果;同时采用流式细胞术检测细胞凋亡率;实时荧光定量RT-PCR法检测COX-2 mRNA的表达;分光光度法检测Caspase-3的活性.结果 姜黄素、顺铂和塞来昔布组均能抑制SGC-7901细胞的增殖,且呈浓度依赖性;姜黄素与顺铂或塞来昔布联用时可增强这种抑制,表现为协同作用.上述三种药物均能诱导胃癌SGC-7901发生凋亡,两药联用组的细胞凋亡率较单药作用组均显著升高（均P＜0.01）.单药作用组细胞中COX-2 mRNA的表达较阴性对照组均显著下降（均P＜0.01）.单药作用组细胞中Caspase-3的活性较阴性对照组均显著升高（均P＜0.01）.结论 在一定药物浓度范围内,姜黄素、顺铂和塞来昔布均能抑制胃癌SGC-7901细胞的增殖、诱导其凋亡.姜黄素与顺铂或塞来昔布联用时均呈现协同作用,这可能与三药均能抑制COX-2 mRNA的表达、提高Caspase-3的活性有关.

Application of median-effect principle in combined chemotherapy for gastric cancer and preliminary exploration of three drugs' anti-cancer mechanisms

Objective To analyze the effects of chemotherapy induced by curcumin combined with cisplatin or celecoxib in the human gastric cancer cell line SGC-7901 cells by using the combination index method of Chou-Talalay （median-effect principle）, and to explore the anti-cancer mechanisms of the three drugs. Methods The experimental groups were divided into six sub-groups： curcumin, cisplatin, celecoxib, combination of curcumin with cisplatin, combination of curcumin with celecoxib; The control group without any drug treatment. MTT assay was performed to detect the proliferation of SGC-7901 cells, and the median-effect principle was used to analyze the effects of their combinations. Flow cytometry was performed to detect the apoptosis rate. The expression of COX-2 mRNA was analyzed by fqRT-PCR. The activation of Caspase-3 was detected by spectrophotometry. Results Each of curcumin, cisplatin and celecoxib could inhibit the proliferation of SGC-7901 cells in a concentration-dependent manner. The combination of curcumin with cisplatin or celecoxib could strengthen the depressive effect. Synergistic effects were detected in these combinations. All of the three drugs could induce apoptosis and the apoptosis rate of the two drugs treated groups was significantly higher than the one drug treated groups （all P 〈0.01）, The expression of COX-2 mRNA in cells was lower in the drugs treated groups than in negative control group （all P 〈0.01）, The activation of Caspase-3 in cells was higher in the drugs treated groups than in negative control group （all P 〈0.01）. Conclusion Within a certain concentration, each of curcumin, cisplatin and celecoxib could inhibit the proliferation of gastric cancer cells SGC-7901 and induce apoptosis. Syner- gistic effects were detected in the combination of curcumin and cisplatin or celecoxib, perhaps correlated with that all the three drugs could inhibit the expression of COX-2 mRNA and increase the activation of Caspase-3.