【摘要】 目的研究热休克对人肝癌HepG2细胞耐药性的影响,探讨合用槲皮素(Qu)能否提高肝癌细胞热化疗的疗效。方法42℃恒温水浴法热休克传代人肝癌细胞系HepG2细胞90min。MTT检测半数抑制浓度(IC50),求得耐药倍数、增敏倍数;荧光染色检测凋亡率;流式细胞术检测HSP70和P-gp表达率。结果Qu能诱导HepG2细胞凋亡。HepG2细胞热休克诱导后4h对多柔比星ADM耐药性升高2.78倍(P<0.05);HSP70阳性细胞数升高,4h达到11.47%,升高近1倍(P<0.01);P-gp阳性细胞数12h达到96.31%,升高近2倍(P<0.01);热休克前应用Qu能有效抑制热休克诱导HSP70和P-gp的过量表达,抑制细胞对ADM耐药性的产生,起增敏作用(P<0.05),呈浓度依赖性。结论槲皮素可阻断热休克诱导HepG2细胞HSP70和P-gp的过表达,抑制耐药性的产生,起到热化疗的增敏作用,可成为肿瘤耐药逆转剂。更多还原

【Abstract】 Objective To study whether heat shock could induce the drug resistance of HepG2 cells to ADM and whether quercetin (Qu) could inhibit the drug resistance and increase the effect of hyperthermia and chemotherapy on human heptocarcinoma cells. Methods HepG2 cells were shocked being at 42℃ stably for 90 min. MTT was used to detect the half growth inhibition concentration (IC50). Then we calculated the drug resistance times and sensitized times. Flurorescence staining was used to detect the percentage of apoptosis. Flow cytometry was used to detect the expressions of HSP70 and P-gp in hepG2 cells. Results The apoptosis of HepG2 cells could be induced by Qu. After heat shock, the drug resistance of HepG2 cells to ADM increased about 2.78 times (P<0.05), and the percentage of HSP70 positive cells came to a climax (11.47 %) at 4 h increasing about 1 fold (P<0.01), and the percentage of cells with P-gp positive came to a climax (96.31 %) at 12 h increasing about 2 fold (P<0.01). However, when Qu was used before heat shock the overexpressions of HSP70 and P-gp induced by heat shock could be inhibited effectively by Qu, and the drug resistance of cells to ADM was inhibited and the effect of ADM was sensitized by Qu in a dose-dependent manner (P<0.05). Conclusions Quercetin can inhibit the overexpressions of HSP70 and P-gp in HepG2 cells induced by heat shock. Quercetin can inhibit drug resistance induced by heat shock and sensitize the effect of hyperthermia and chemotherapy. Quercetin is possible to be a reversal agent of drug resistance.更多还原