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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。
The occurrence of multi-drug resistance (MDR) in the course of cancer therapy will reduce the efficacy of chemotherapy drugs. High expression of transporter is an important mechanism of tumor MDR. P-glycoprotein (P-glycoprotein, P-gp), as a member of the ABC (ATP-binding cassette) transporter family, is often overexpressed in drug-resistant tumor cells and causes MDR. In order to overcome MDR caused by P-gp, antineoplastic drugs can be administered simultaneously with P-gp inhibitors. Piperine and (R) - (+) - citronellal are P-gp inhibitors derived from the daily diet. In the present study, we evaluated the reversal of drug resistance of piperine and (R) - (+) - citronellal in multidrug resistant breast cancer cell line MCF-7 / DOX cells. After 72 hours of incubation cytotoxicity results showed that both piperine and (R) - (+) - citronellal decreased the drug resistance of MCF-7 / DOX cells. In addition, piperine down-regulated the mRNA level of MDR1 gene in a concentration-dependent manner, while (R) - (+) - citronellal had no effect on the m RNA level of MDR1 gene. Therefore, piperine and (R) - (+) - citronellaldehyde could reverse the MDR of MCF-7 / DOX cells in a concentration-dependent manner. The reversal effect of piperine was related to the downregulation of MDR1 mRNA.