金丝桃苷对小鼠S_(180)肿瘤细胞获得性多药耐药相关因子表达的影响

Effects of hyperin on expression of correlation factor of multidrug-resistant in mouse S_(180) tumor cells

目的:探讨金丝桃苷干预化疗诱导的肿瘤多药耐药(MDR)的分子机制,以指导临床应用金丝桃苷来逆转肿瘤多药耐药的产生。方法:建立小鼠S180肿瘤细胞多药耐药模型,随机分为模型组、环磷酰胺(CTX)组、CTX+金丝桃苷组、金丝桃苷组,连续给药2周,观察各组瘤体大小,计算抑瘤率。流式细胞仪观察各组细胞凋亡率、P-糖蛋白(P-gp)、肺耐药相关蛋白(LRP)、凋亡促进因子Fas及抗凋亡因子bcl-2的表达。结果:CTX+金丝桃苷组抑瘤率、细胞凋亡率、Fas表达率均较CTX组显著增高,而P-gp、LRP、bcl-2表达率均较CTX组显著降低,差异均有统计学意义(P<0.01)。结论:金丝桃苷有逆转小鼠S180肿瘤获得性多药耐药的作用与降低P-gp、LRP、bcl-2表达,提高Fas表达有关。

OBJECTIVE To investigate the molecular mechanisms of multidrug resistance（MDR）in hyperin chemotherapy and to provide data to guide clinical administration of hyperin to reverse MDR.METHODS S180 multidrug resistance mouse models were constructed and randomly divided into MDR model,cyclophosphamide（CTX）,CTX＋hyperin and hyperin groups,and drugs were administered for 2 weeks,to observe the tumor sizes and calculate tumor inhibition rates.The apoptosis rate,expression of P-gp,LRP,Fas and bcl-2 were measured by flow cytometry.RESULTS Tumor inhibition rate,apoptosis rate and expression of Fas in CTX＋hyperin group were significant higher than in CTX group（P0.01）.Expressions of P-gp,LRP and bcl-2 in CTX＋hyperin group were significant lower than in CTX group（P0.01）.CONCLUSION Hyperin can reverse the acquired multidrug resistance of mouse S180 tumor cells probably by increases Fas expression and lowering expressions of P-gp,LRP and bcl-2.