健脾中药胃肠安与5-FU相互作用的中效原理评价  

The Evaluation on Median Effect Principle of the Interaction Between Jianpi Traditional Chinese Medicine Weichang'an and 5-FU

作　　者：邹煜明[1] 陈伟霞[1] 牛垚飞 唐亚荣 陈彬[4] 徐燕[1] 赵爱光[1] ZHOU Yuming;CHEN Weixia;NIU Yaofei;JANG Yarong;CHEN Bing;XU Yan;ZHAO Aiguang(Longhua Hospital Affiliated to Shanghai University of Chinese Medicine,Shanghai China 200032;People's Hospital of HenanProvince,Zhengzhou Henan China 450003;Integration of Traditional and Western Medicine Hospital of Shanghai Jinshan,Shanghai China 201501;Putuo Hospital Affiliated to Shanghai University of Chinese Medicine,Shanghai China 200062)

机构地区：[1]上海中医药大学附属龙华医院,上海200032 [2]河南省人民医院,河南郑州450003 [3]上海市金山区中西医结合医院,上海201501 [4]上海中医药大学附属普陀医院,上海200062

出　　处：《中医学报》2019年第2期333-338,共6页Acta Chinese Medicine

基　　金：国家中医药管理局国家中医临床研究基地业务建设科研专项项目(JDZX2015068);国家科技部重点研发计划项目(2017YFC1700605)

摘　　要：目的:采用中效原理探讨健脾复方胃肠安(Weichang′an,WCA)联合5-氟尿嘧啶(5-fluorouracil,5-FU)的相互作用,并观察体外对胃癌细胞MKN45的增殖、凋亡等生物学行为的影响。方法:本实验选取人胃癌细胞株MKN45为实验对象,用不同浓度的WCA、5-FU单药和两药11浓度配比联合作用于胃癌细胞(24 h,48 h,72 h),Cell Counting Kit-8(CCK-8)法检测药物对胃癌细胞抑制作用。根据中效原理分析两药联合作用的效应(Fa)与合用指数(CI)的关系,判定药物间的相互作用。以药物单用及合用的1/2倍中效浓度作用于MKN45细胞,流式细胞凋亡检测法评价药物对细胞周期、凋亡的影响,Hoechst 33258荧光染色观察细胞凋亡形态。结果:两种药物单独应用或联合应用均对胃癌细胞有明显的抑制作用,并且呈剂量效应依赖关系。由中效原理计算可知,两药联合应用抑制胃癌细胞增殖作用增强,存在协同效应。细胞周期检测提示WCA与5-FU均阻滞细胞周期于S期,两药联用时更加显著;流式细胞凋亡检测与Hoechst染色均发现单药组细胞凋亡现象较对照组明显,而联合组细胞凋亡现象更加明显。结论:健脾中药WCA与5-FU联合应用对胃癌MKN45细胞产生协同效应。Objective:To discuss the interaction between invigorating spleen Chinese medicine and 5-FU using the median effect principle and observe the effect of in vitro on proliferation,apoptosis and other biological behaviors of gastric cancer cell MKN45.Methods:In this experiment,human gastric cancer cell line MKN45 was selected as the experimental object,and different concentrations of WCA,5-FU single drug and 1■1 concentration ratio of the two drugs were combined to act on gastric cancer cells(24 h,48 h,72 h).Cell Counting Kit-8(CCK-8) method was used to detect the relationship between the inhibition of drugs on gastric cancer cells.According to the median effect principle,the relationship between the effect(Fa) of the combined action of the two drugs and the combination index(CI) was analyzed to determine the interaction between the drugs.The MKN45 cells were treated with 1/2 times the median concentration of the drugs used alone and in combination.The effects of drugs on cell cycle and apoptosis were detected by flow cytometry.The morphology of apoptosis was observed by Hoechst 33258 fluorescence staining.Results:Both drugs alone or in combination had obvious inhibitory effect on gastric cancer cells and show a dose-effect dependent relationship.From the calculation of the medium efficiency principle,the combined application of the two drugs enhances the inhibition of gastric cancer cell proliferation and had a synergistic effect.Cell cycle test showed that WCA and 5-FU both blocked cell cycle in S phase,and the combination of WCA and 5-FU was more significant.Flow cytometry and Hoechst staining showed that apoptosis in the single drug group was more obvious than that in the control group,while apoptosis in the combined group was more obvious.Conclusion:Combined application of invigorating spleen Chinese medicine and 5-FU Jianpi compound WCA and 5-FU has a synergistic effect on MKN45 cells of gastric cancer.

关 键 词：胃癌 胃肠安 5-氟尿嘧啶 中效原理 协同效应 

分 类 号：R273[医药卫生—中西医结合]