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目的:利用中效原理评价藤黄酸(gambogic acid,GA)与5-氟尿嘧啶(5-FU)之间的相互作用,并探讨其相互作用的可能机制。方法:采用MTT法测定GA、5-FU单药及联合作用于指数增殖期BGC-823、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;RT-qPCR方法检测并比较GA作用前后5-FU药物疗效相关基因胸苷酸合成酶(TS)和乳清酸磷酸核糖转移酶(OPRT)mRNA及肿瘤细胞凋亡抑制基因Survivin mRNA的表达。结果:GA联合5-FU作用于BGC-823肿瘤细胞株可产生较好的协同效应,GA作用后TS及Survivin mRNA表达明显下调。结论:GA与5-FU联合应用作用于BGC-823细胞可产生较好协同效应,下调肿瘤细胞药物疗效相关基因的表达及凋亡抑制基因的表达可能是GA与5-FU两者间产生协同效应的机制之一。
OBJECTIVE: To evaluate the interaction between gambogic acid (GA) and 5-fluorouracil (5-FU) and explore the possible mechanism of its interaction by using the principle of intermediate efficiency. Methods: MTT assay was used to determine the effect of GA and 5-FU on the proliferation of BGC-823 and MKN-28 cells. Statistical analysis was made on the effect of single agent and combination therapy on the growth of tumor cells (Fa) -combination index (CI), and determine the interaction between drugs; RT-qPCR method to detect and compare the effect of 5-FU before and after the treatment of GA gene thymidylate synthase (TS) and the expression of OPT mRNA and Survivin mRNA in tumor cells. Results: The combined effect of GA and 5-FU on BGC-823 cell line could produce better synergistic effect, and the expression of TS and Survivin mRNA was down-regulated after treated with GA. CONCLUSION: Combination of GA and 5-FU on BGC-823 cells can produce better synergistic effect, down-regulate the expression of drug-related genes and the expression of apoptosis-suppressing genes in tumor cells, which may be due to the synergism between GA and 5-FU One of the mechanisms of effect.