雷帕霉素靶蛋白抑制剂对人黑素瘤细胞耐药性的影响  

The effect of mTOR inhibitors on overcoming multidrug resistance in human melanoma cells

作　　者：姚战非[1] 张雪梅[1] 乌云[1] 

机构地区：[1]内蒙古民族大学附属医院皮肤科,内蒙古呼和浩特028000

出　　处：《临床皮肤科杂志》2014年第3期136-139,共4页Journal of Clinical Dermatology

摘　　要：目的:探讨哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)抑制剂对人黑素瘤细胞株A375细胞多药耐药的逆转作用及机制。方法:雷帕霉素(rap★ycin,R APA)作用于黑素瘤A375细胞后,通过Westem blot法检测细胞mTOR表达量及磷酸化水平;检测顺铂对黑素瘤细胞生长的抑制作用;流式细胞术检测黑素瘤细胞内罗丹明-123的蓄积;Westem blot检测细胞多药耐药蛋白(multidrug resistance p★tein l,MDR1)、多药耐药相关蛋白(multidmg resistance-associated protein-1,MRP1)表达水平。结果:RAPA可抑制mTOR的活性,提高黑素瘤细胞对顺铂的药物敏感性,经10 nmol/L和20nmol/L RAPA作用后,顺铂对黑素瘤细胞的抑制率升高,黑素瘤细胞中罗丹明-123荧光强度分别提高了1.67倍和2.05倍,MDR1和MRP1蛋白表达水平显著下降。结论:mTOR抑制剂可逆转黑素瘤A375细胞耐药性,降低细胞MDR1和MRP1蛋白表达,为临床黑素瘤的治疗提供了线索。Objective： To investigate the effect and mechanism of mTOR （mammalian target of rapamycin, mTOR） inhibitor on overcoming muhidrug resistance in A375 human melanoma cells. Methods： A375 melanoma cells were treated with mTOR inhibitor, rapamycin. The levels of mTOR expression and phosphorylation were examined by western blot; The growth inhibition of cisplatin on melanoma cells was measured with MTS assay; Rhodamine-123 accumulation was assessed using flow cytometry; Expression levels of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein-1 （MRP1） were detected by western blot. Results： mTOR inhibitor inhibited the phosphorylation of mTOR and enhanced the chemosensitivity of melanoma cells to cisplatin. In addition to the increase in the inhibition rates of cisplatin on melanoma cells, both 10 nmol/L and 20 nmol/L rapamycin also increased the intensity of rhodamine-123 fluorescence by 1.67 and 2.05 times, respectively. However, the levels of MDR1 and MRP1 protein were significantly decreased as compared with the control group. Conclusion： mTOR inhibitor can reverse the drug resistance of A375 melanoma ceils and reduce cellular MDR1 and MRP expression. These findings could lead to a new strategy for treating malignant melanoma.

关 键 词：黑素瘤 雷帕霉素靶蛋白抑制剂 耐药性 

分 类 号：R739.5[医药卫生—肿瘤]