摘要
Multidrug resistance （MDR） in tumor cells can reduce the efficacy of chemotherapy. Overexpression of transporters is an important mechanism for MDR. P-glycoprotein （P-gp） is an ATP-binding cassette transporter frequently expressed in multidrug resistant tumor cells, inducing MDR. To reverse P-gp dependent MDR, anticancer drugs can be administered with P-gp inhibitors. Piperine and （R）-（＋）-citronellal both are P-gp inhibitors from dietary sources. In the present study, we aimed to evaluate the MDR reversal effects of piperine and （R）-（＋）-citronellal in multidrug resistant MCF-7/DOX cells. The results of cytotoxicity studies indicated that piperine and （R）-（＋）-citronellal both could abate the resistance of MCF-7/DOX after 72-h incubation. After 72-h incubation, piperine could dose-dependently down-regulate the MDR1 expression at the mRNA level, while （R）-（＋）-citronellal had no effect on the MDR1 expression. Therefore, piperine and （R）-（＋）-citronellal both could reverse MDR in MCF-7/DOX cells, and the reversal effect ofpiperine was related to dose-dependent down-regulation of the MDR1 expression at the mRNA level.
肿瘤治疗过程中多药耐药(MDR)的发生会降低化疗药物的疗效。转运体的高表达是引起肿瘤MDR的重要机制。P糖蛋白(P-glycoprotein,P-gp)作为ABC(ATP-binding cassette,ABC)转运体家族的一员,经常在耐药肿瘤细胞中高表达,引起MDR。为了克服P-gp引起的MDR,抗肿瘤药物可以与P-gp抑制剂同时给药。胡椒碱和(R)-(+)-香茅醛都是来源于日常饮食的P-gp抑制剂。在本研究中我们评价了胡椒碱和(R)-(+)-香茅醛在多药耐药乳腺癌细胞系MCF-7/DOX细胞中的耐药逆转作用。经过72小时的孵育后,细胞毒性研究结果表明胡椒碱和(R)-(+)-香茅醛均能降低MCF-7/DOX细胞的耐药性。此外,胡椒碱可以浓度依赖性地下调MDR1基因的mRNA水平,而(R)-(+)-香茅醛对MDR1基因的m RNA水平没有影响。因此,胡椒碱和(R)-(+)-香茅醛可以浓度依赖性地逆转MCF-7/DOX细胞的MDR,胡椒碱的耐药逆转作用与下调MDR1基因的mRNA水平相关。
