锌原卟啉ZnPPⅨ对Bel/FU肝癌耐药细胞株p-糖蛋白及化疗敏感性的影响

ZnPP Ⅸ's effect on p-glycoprotein expression and chemosensitivity of drug-resistant hepatic carcinoma cell line

目的:评估锌原卟啉(ZnPP)Ⅸ对Bel/FU肝癌耐药细胞株p-糖蛋白(p-glycoprotein,p-GP)的影响,探讨ZnPPⅨ作为化疗耐药逆转剂可能性及相关作用机制。方法:不同浓度的ZnPPⅨ作用于Bel/FU肝癌化疗耐药细胞株,MTT法检测细胞株对化疗药物的半数抑制浓度(IC50)、Western blot检测p-GP表达量、罗丹明潴留试验检测p-GP药物外排功能。结果:ZnPPⅨ作用于Bel/FU细胞诱导24 h后,化疗药物IC50值均显著降低,p-GP表达量明显降低(P均<0.01),p-GP药物外排功能减弱。结论:ZnPPⅨ可通过影响p-GP蛋白质水平的表达,减弱p-GP药物外排功能,使肝癌耐药细胞株的化疗敏感性降低;ZnPPⅨ可作为一种潜在的化疗耐药逆转剂。

Objective： To evaluate ZnPP Ⅸ＇s effect on the expression of p-glycoprotein（P-GP）and the chemosensitivity of drug-resistant hepatic carcinoma Bel/Fu cell line,and to explore the relevant regulating mechanism.Methods： After Bel/FU cells being induced by different gradient concentrations of ZnPP Ⅸ for 24 h,MTT assay was carried out to detect the sensitivity of Bel/Fu;P-glycoprotein protein level was determined by Western blot analysis;Rhodamine123 retention fluorescent intensity measured by flow cytometry was used to detect the function of p-GP.Results： After Bel/FU cells being dealt with ZnPP Ⅸ for 24 h,there were significant differences in 50% inhibiting concentration（IC50） of chemical drugs between control groups and contrast group.IC50 of control groups decreased obviously.Meanwhile,p-GP protein level expression in the cells of control groups were observably lower than that in contrast group.The curve of Rhodamine123 retention fluorescent intensity in the control cells shift to the right,which indicated that the efflux pump function of p-GP was weakened.Conclusions： ZnPP Ⅸ can increase the chemosensitivity of Bel/FU cell line,which relates with its action in down-regulation of P-glycoprotein expression.ZnPP Ⅸ may be a new kind of agent reversing multidrug resistance of hepatic carcinoma cells.