Institute of Experimental Physiology, Faculty of Biochemical and Pharmaceutical Science, Rosario National University, Rosario, Argentina.
Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Curr Med Chem. 2019;26(7):1224-1250. doi: 10.2174/0929867325666180105103637.
For most cancers, the treatment of choice is still chemotherapy despite its severe adverse effects, systemic toxicity and limited efficacy due to the development of multidrug resistance (MDR). MDR leads to chemotherapy failure generally associated with a decrease in drug concentration inside cancer cells, frequently due to the overexpression of ABC transporters such as P-glycoprotein (P-gp/MDR1/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs), and breast cancer resistance protein (BCRP/ABCG2), which limits the efficacy of chemotherapeutic drugs. The aim of this review is to compile information about transcriptional and post-transcriptional regulation of ABC transporters and discuss their role in mediating MDR in cancer cells. This review also focuses on drug resistance by ABC efflux transporters in cancer cells, particularly hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) cells. Some aspects of the chemotherapy failure and future directions to overcome this problem are also discussed.
对于大多数癌症，尽管化疗存在严重的不良反应、全身毒性和疗效有限，因为多药耐药性（MDR）的发展，但它仍然是治疗的首选。MDR 通常会导致化疗失败，这与癌细胞内药物浓度降低有关，这通常是由于 ABC 转运蛋白（如 P 糖蛋白（P-gp/MDR1/ABCB1）、多药耐药相关蛋白（MRPs/ABCCs）和乳腺癌耐药蛋白（BCRP/ABCG2）的过度表达，这些蛋白限制了化疗药物的疗效。本综述的目的是汇编关于 ABC 转运蛋白转录和转录后调节的信息，并讨论它们在介导癌细胞 MDR 中的作用。本综述还重点介绍了 ABC 外排转运蛋白在癌细胞中的耐药性，特别是肝癌（HCC）和结直肠癌（CRC）细胞。还讨论了化疗失败的一些方面以及克服这个问题的未来方向。
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