肿瘤细胞高表达P糖蛋白(P-gp)会抑制化疗的疗效,导致肿瘤耐药,而P-gp抑制剂可逆转P-gp介导的肿瘤耐药.辣椒素是辣椒的主要活性成分,也是P-gp抑制剂.本研究旨在初步探讨辣椒素对多柔比星(DOX)耐药的乳腺癌MCF-7/DOX细胞的耐药逆转作用.细胞毒性研究结果表明,长期处理72 h后,辣椒素(50 μM)可以逆转MCF-7/DOX细胞对多柔比星的耐药(逆转倍数为4.68倍),并浓度依赖性地下调MDR1基因mRNA的表达.在短期培养3h后,辣椒素可逆地、浓度依赖性地增加了DOX在MCF-7/DOX细胞中的蓄积,对DOX在细胞内亚细胞分布的影响不同于阳性对照药维拉帕米.辣椒素也能浓度依赖性地抑制线粒体生成ATP.综上所述,辣椒素能够逆转MCF-7/DOX细胞对DOX的耐药,可成为一种很有前途的逆转多药耐药的先导化合物.“,”Overexpression of P-glycoprotein (P-gp),encoded by the MDR1 gene,in tumor cells curtails the efficacy of chemotherapy,leading to multidrug resistance (MDR),which can be reversed by the P-gp inhibitor.Capsaicin,the principal pungent component of hot chili,is a reported P-gp inhibitor with anti-cancer properties.In the present study,we aimed to evaluate the MDR reversal effect of capsaicin.The MCF-7/DOX cells were treated with capsaicin for a short term (3 h) or long term (72 h).The cytotoxicity studies were completed by using the SRB method.RT-PCR method was utilized to evaluate the effect of capsaicin on the expression of MDR1 at the mRNA level.The accumulation and subcellular distribution studies were implemented to further investigate the reversal effect of capsaicin.The effect of capsaicin on the ATP production of mitochondria was also evaluated.The results of the cytotoxicity study indicated that capsaicin (50 μM) reversed the resistance of MCF-7/DOX cells to doxorubicin (DOX) with the reversal fold of 4.68,and concentration-dependently down-regulated the expression of MDR 1 at the mRNA level after long-term(72 h) incubation.After short-term (3 h) incubation,capsaicin reversibly and concentration-dependently increased the accumulation of DOX into MCF-7/DOX cells and induced a different subcellular distribution of DOX compared with verapamil as a positive control.The ATP production of mitochondria was also concentration-dependently inhibited by capsaicin.In conclusion,capsaicin was capable of reversing the resistance of MCF-7/DOX cells to DOX,making it a promising lead compound for MDR reversal.