姜黄素对Bel7402/5-Fu细胞系多药耐药逆转作用的实验研究

目的研究姜黄素对肝癌耐药细胞系Bel7402/5-Fu多药耐药的逆转作用。方法采用5-氟脲嘧啶(fluorouracil,Fu)药物浓度梯度递增法诱导建立肝癌耐药细胞亚系Bel7402/5-Fu;四甲基偶氮唑盐比色(methyl thiazolyl tetrazolium,MTT)法检测肝癌细胞系Bel7402和肝癌耐药细胞系Bel7402/5-Fu对6种化疗药物的敏感性,计算两组细胞系对6种化疗药物的半数抑制剂量(IC50)和耐药指数(RI);MTT法检测姜黄素、5-Fu、姜黄素和5-Fu合用对肝癌耐药细胞系Bel7402/5-Fu抑制率的差异;流式细胞仪检测姜黄素、5-Fu、姜黄素和5-Fu合用对肝癌耐药细胞系Bel7402/5-Fu凋亡的影响。结果肝癌耐药细胞系Bel7402/5-Fu对多种化疗药物表现出耐药性,其中对5-Fu耐药指数最高,为(109.55±14.30)倍。5、10、20μg/mL浓度的姜黄素联合5-Fu(1/2IC50浓度)对细胞的抑制率分别为(21.47±1.49)%、(27.10±2.32)%、(59.37±2.45)%。5、10、20μg/mL浓度的姜黄素联合5-Fu作用后Bel7402/5-Fu的凋亡率分别为(30.92±2.10)%、(44.87±2.24)%、(50.36±2.58)%,明显高于姜黄素组和5-Fu组,且姜黄素浓度在0～20μg/mL范围内,凋亡率随姜黄素浓度增加而增大。结论姜黄素能促进肝癌耐药细胞系Bel7402/5-Fu的凋亡,同时具有良好的逆转其耐药性的效果。

Reversing Effects of Curcumin on Multi-drug Resistance of Bel7402/5-Fu Cell Line

Objective To investigate the reversing effects of curcumin on hepatocellular carcinoma drug resistance Bel7402/5-Fu cell line.Methods Through the exposure to gradual increased concentrations of 5-fluorouracil(5-Fu),the cell line Bel7402 was induced to establish a multi-drug resistant sub-cell line Bel7402/5-Fu.The sensitivity to 6 chemotherapeutics of Bel7402 and Bel7402/5-Fu were detected using methyl thiazolyl tetrazolium(MTT) assay.The 50% inhibitory concentration(IC50) and resistant index(RI) were calculated.The differences of the inhibition ratio of Bel7402/5-Fu by curcumin,5-Fu,curcumin combined with 5-Fu were detected using MTT assay.The effects of curcumin,5-Fu,curcumin combined with 5-Fu on the Bel7402/5-Fu apoptosis were detected using flow cytometry.Results The Bel7402/5-Fu cell line showed multi-drug resistance(MDR) to various chemotherapeutics,with the highest RI shown of 5-Fu(being 109.55±14.30 times).The inhibition ratio of 5,10,and 20 μg/mL curcumin combined with 5-Fu(50% IC50) was respectively 21.47%±1.49%,27.10%±2.32%,and 59.37%±2.45%.The Bel7402/5-Fu apoptosis ratio of 5,10,and 20 μg/mL curcumin combined with 5-Fu(50% IC50) was 30.92%±2.10%,44.87%±2.24%,and 50.36%±2.58%,respectively,which was obviously higher than that of the curcumin group and the 5-Fu group.Besides,the apoptosis rate increased along with increased curcumin concentration in the range of 0-20 μg/mL.Conclusion Curcumin could induce the apoptosis of Bel7402/5-Fu.Meanwhile,it showed favorable reversing effects on MDR.