Nuclear receptors in the multidrug resistance through the regulation of drug-metabolizing enzymes and drug transporters.
Nuclear receptors in the multidrug resistance through the regulation of drug-metabolizing enzymes and drug transporters.
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DOI：
10.1016/j.bcp.2012.01.030
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发表时间：
2012-04-15
影响因子：
5.8
通讯作者：
Nie, Daotai
中科院分区：
文献类型：
--
作者：
Chen, Yakun;Tang, Yong;Guo, Changxiong;Wang, Jiuhui;Boral, Debasish;Nie, Daotai
化疗是癌症三种最常见的治疗方式之一。然而，其疗效受到多药耐药癌细胞的限制。药物代谢酶（DME）和外排转运蛋白促进化疗剂的代谢、消除和解毒。因此，DME和外排转运蛋白水平的升高降低了化疗药物的治疗效果，并且通常导致治疗失败。核受体，特别是甾烷X受体（PXR，NR 1 I2）和组成型雄烷激活受体（CAR，NR 1 I3），由于其在异生物质代谢和清除中的作用以及它们在化疗期间的多药耐药（MDR）的发展中的作用而日益被认识。混杂的异生物质受体，包括PXR和CAR，支配编码I相DME、II相DME和外排转运蛋白的广谱靶基因的诱导表达。包括我们在内的许多研究小组最近进行的研究表明，PXR和CAR在各种人类癌症（包括前列腺癌、结肠癌、卵巢癌和食管鳞状细胞癌）的MDR发展中起关键作用。因此，PXR/CAR表达水平和/或活化状态可以预测预后并鉴定经受化疗的患者的耐药性风险。此外，当与激活PXR/CAR的现有化学治疗剂组合使用时，PXR/CAR拮抗剂是可行且有前景的选择，其可用于克服或至少减弱癌细胞中的MDR。
Chemotherapy is one of the three most common treatment modalities for cancer. However, its efficacy is limited by multidrug resistant cancer cells. Drug metabolizing enzymes (DMEs) and efflux transporters promote the metabolism, elimination, and detoxification of chemotherapeutic agents. Consequently, elevated levels of DMEs and efflux transporters reduce the therapeutic effectiveness of chemotheraputics and, often, lead to treatment failure. Nuclear receptors, especially pregnane X receptor (PXR, NR1I2) and constitutive androstane activated receptor (CAR, NR1I3), are increasingly recognized for their role in xenobiotic metabolism and clearance as well as their role in the development of multidrug resistance (MDR) during chemotherapy. Promiscuous xenobiotic receptors, including PXR and CAR, govern the inducible expressions of a broad spectrum of target genes that encode phase I DMEs, phase II DMEs, and efflux transporters. Recent studies conducted by a number of groups, including ours, have revealed that PXR and CAR play pivotal roles in the development of MDR in various human carcinomas, including prostate, colon, ovarian, and esophageal squamous cell carcinomas. Accordingly, PXR/CAR expression levels and/or activation statuses may predict prognosis and identify the risk of drug resistance in patients subjected to chemotherapy. Further, PXR/CAR antagonists, when used in combination with existing chemotherapeutics that activate PXR/CAR, are feasible and promising options that could be utilized to overcome or, at least, attenuate MDR in cancer cells.
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影响因子：
4.8
作者：
Barbier, O;Duran-Sandoval, D;Staels, B
通讯作者：
Staels, B
DOI：
10.1073/pnas.95.21.12208
发表时间：
1998-10-13
影响因子：
11.1
作者：
Bertilsson, G;Heidrich, J;Berkenstam, A
通讯作者：
Berkenstam, A
影响因子：
8.8
作者：
Chakraborty, S.;Kanakasabai, S.;Bright, J. J.
通讯作者：
Bright, J. J.
影响因子：
3.6
作者：
Chen, Yakun;Tang, Yong;Nie, Daotai
通讯作者：
Nie, Daotai
影响因子：
56.9
作者：
BROWN, MS;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL