孕烷X受体和组成型雄甾烷受体在肿瘤多药耐药中的研究进展

摘要

Chemotherapy is one of the three most common treatment modalities for cancer .However , chemotherapy as current firstline therapy induces significant side effects and limited efficacy ,leading to multidrug resistance and fast recurrence challenging the patient survival rate .Drug metabolizing enzymes ( DMEs) and efflux transporters promote the metabolism,clearance,and detoxification of chemotherapeutic agents .Nuclear receptors, especially pregnane X receptor (PXR,NR112)and constitutive androstane activated receptor (CAR,NR113),reg-ulate the expressions of target genes that could encode phase I DMEs ,phase II DMEs,and efflux transporters in the development of multidrug resistance ( MDR) during chemotherapy .Recent studies have revealed that PXR and CAR play pivotal roles in MDR of various human carcinomas .And their expressve levels or activation statuses could predict the risk of drug resistance in the patients subjected to chemotherapy .Accordingly ,PXR/CAR antag-onists,combining with existing chemotherapeutics that activate PXR /CAR,are promising options that could over-come MDR in cancer.%化疗是当今最常见的三种抗癌疗法之一。然而化疗作为一线抗癌疗法因其疗效有限并会引起严重的副作用，使有效性受限，导致多药耐药（ MDR）以及肿瘤复发。药物代谢酶（ DMEs）和转运体会分解、消除化疗药物。在多药耐药发展过程中（化疗期间）核受体，尤其是孕烷X受体（ PXR，NR112）和组成型雄甾烷受体（CAR，NR113），调控编码DMEs一相酶、二相酶和转运体靶基因的诱导表达。最近的研究结果显示PXR和CAR在人类各种肿瘤组织多药耐药的发展中起关键作用。通过PXR/CAR表达水平或活化状态可预测化疗患者产生药物抵抗的风险性。最终PXR/CAR拮抗剂，在与可激活PXR/CAR化疗药物并用时，有望成为用来克服肿瘤细胞多药耐药的选择。