姜黄素逆转P-gp介导卵巢癌多药耐药机制的研究

Effect of curcumin on reverse P-gp mediated mechanism of multidrug resistance in ovarian cancer

目的探讨姜黄素对P糖蛋白（P—gP）介导的卵巢癌多药耐药的逆转作用及其可能机制。方法采用二苯基溴化四氮唑蓝（MTT）法检测人卵巢癌癌细胞株加药后的增殖，碘化丙啶（PI）染色法检测细胞凋亡率，western blot法检测P—Akt和P-gP的表达量。结果姜黄素合用顺铂处理细胞（OVCAR-3／DDP细胞株）48h，顺铂的浓度在0．05—5μg／ml时，加入姜黄素25μmol／L，耐药细胞生存率下降明显（P〈0．05），尤以顺铂0．25μg／ml和姜黄素25μmol／L作用时耐药细胞生存率下降最明显。单用顺铂组细胞的凋亡率为（13．2±2．5）％，采用在顺铂基础上联合使用姜黄素后细胞凋亡率为（21．8±3．5）％，与单独使用顺铂相比，顺铂与姜黄素联合使用诱导细胞凋亡的作用显著增强（P〈0．05）。与单用顺铂0．25μg/ml相比，联合使用姜黄素后p-Akt和P-gP的表达量明显降低（P〈0．05），2组间Akt的表达量差异无统计学意义（P〉0．05）。结论姜黄素不增加顺铂对OVCAR-3细胞毒性作用；对于OVCAR-3／DDP细胞株，姜黄素明显增加顺铂细胞毒性；姜黄素明显抑制了p-Akt和P—gP蛋白的表达。姜黄素可能通过抑制Akt信号通路降低P—gP的表达进而逆转多药耐药。

Objective To investigate the effects of curcumin on P glycoprotein （P-gp） reversal effect of ovarian cancer mediated muhidrug resistance and its possible mechanism. Methods For determination of drugs in vitro cytotoxicity by MT]＂ assay, apoptosis was detected by PI staining, expression of p-Akt and P-gp for detection by Western blot method. Re- suits Curcumin did not increase cisplatin cytotoxicity on OVCAR-3 ; for OVCAR-3/DDP cells, curcumin significantly in- creased the cytotoxieity of cisplatin;inhibition of expression of p-Akt and P-gp protein were inhibited by curcumin. Con- clusion Curcumin can inhibit Akt signaling pathway by decreasing the expression of P-gp and reversal of multidrug re- sistance.