藤黄酸与5-FU相互作用的中效原理评价

Application of median-effect principle in quantitative analysis of natural interaction between gambogic acid and fluracil

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 assess the natural interaction between gambogic acid （GA） and fluracil （5-FU） in cancer treatment, and investigate the influence of GA on cell apoptosis and drug-associated gene expression. METHODS：The synergistic interaction on human cancer cell lines, such as humman gastric cancer cell lines BGC-823 and MKN-28, was evaluated by using MTT and the combination index （CI） method. The expression of drug-associated genes, i. e. , thymidylate synthase （TS） and orotate phosphoribosyl transferase （OPRT） mRNA, and the apoptotic suppression gene Survivin mRNA of BGC-823 cells with or without GA treatment were measured by real-time quantitative RT-PCR. The median-effect principle was used to analyse the relationship of fa-CI. RESULTS： GA had a synergistic effect on the cytotoxicity of 5-FU in BGC-823 cells. GA decreased the mRNA expressions of TS and Survivin mRNA of BGC-823 cells. CONCLUSIONS： GA appears a promising candidate for combination with 5-FU in cancer chemotherapy. The possible synergistic mechanisms may be related to the downregulation of the drug-associated genes and the apoptotic-inhibi- ted gene expression.