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目的:探讨藤黄酸(gambogic acid,GA)联合奥沙利铂(Oxaliplatin,Oxa)体外对人低分化胃癌细胞株BGC-823和人高分化胃癌细胞株MKN-28的作用及可能机制。方法:采用MTT法测定GA、Oxa单药及联合作用于指数增殖期BGC-823细胞和MKN-28细胞的效应;应用中效原理进行统计分析,绘制单药及联合用药对肿瘤细胞生长的影响曲线,确定联合用药时的效应(Fa)-合用指数(CI)的关系,判定药物间的相互作用;用流式细胞仪检测GA联合Oxa对肿瘤细胞凋亡的影响;采用RT-qPCR Taqman探针方法检测GA对Oxa疗效相关基因ERCC1、BRCA1 mRNA表达的影响,推断GA与Oxa间相互作用的分子机制。结果:GA联合Oxa作用于指数增殖期BGC-823细胞,当Fa=0.10,CI≈1,两药合用效应相加;当Fa>0.10,CI<1,两药合用产生协同效应,凋亡细胞比例明显增加;当Fa<0.10,两药合用产生拮抗效应;GA联合Oxa作用于指数增殖期MKN-28细胞,当Fa=0.50,CI≈1,两药合用效应相加;当Fa>0.50,CI<1,两药合用产生协同效应;当Fa<0.50,两药合用产生拮抗效应;GA联合Oxa作用于BGC-823细胞产生了较好的协同效应。GA作用后BGC-823细胞的ERCC1及BRCA1 mRNA明显下调。结论:影响药物疗效相关基因的表达,可能是GA与Oxa联合应用产生协同效应的机制之一。
OBJECTIVE: To investigate the effect of gambogic acid (GA) combined with oxaliplatin (Oxa) on human poorly differentiated gastric cancer cell line BGC-823 and human well-differentiated gastric cancer cell line MKN-28 and its possible mechanism. Methods: MTT assay was used to determine the effects of single drug combination with GA and Oxa on exponential proliferation of BGC-823 cells and MKN-28 cells. The effect of single drug and combination therapy on tumor cell growth Curve to determine the effect (Fa) - combination index (CI) in the combination therapy to determine the drug interaction; using flow cytometry to detect the effect of GA combined with Oxa on tumor cell apoptosis; using RT-qPCR Taqman The effect of GA on the expression of ERCC1 and BRCA1 mRNA in the curative effect of Oxa and the molecular mechanism of the interaction between GA and Oxa were detected by the needle method. Results: GA combined with Oxa in exponential proliferation BGC-823 cells, when Fa = 0.10, CI≈1, the combined effect of the two drugs added; when Fa> 0.10, CI <1, the two drugs synergistic effect, When Fa <0.10, the combination of two drugs produced antagonistic effect; GA combined with Oxa on exponential proliferation of MKN-28 cells, when Fa = 0.50, CI ≈ 1, the combined effect of the two drugs; CI <1, synergistic effect between the two drugs produced; when Fa <0.50, the two drugs combined antagonistic effect; GA combined Oxa BGC-823 cells produced a good synergistic effect. The effect of GA on ERCC1 and BRCA1 mRNA expression in BGC-823 cells was significantly down-regulated. Conclusion: The expression of genes related to drug therapy may be one of the mechanisms of synergistic effect between GA and Oxa.