Hasanabady Maryam Hosseini, Kalalinia Fatemeh
Department of Biology, Science and Research Branch, Islamic Azad University, Mashhad, Iran.
J Biosci. 2016 Jun;41(2):313-24. doi: 10.1007/s12038-016-9601-5.
Breast cancer resistance protein (BCRP, ABCP or MXR)/ATP-binding cassette subfamily G member 2 (ABCG2) was characterized as a multidrug resistance efflux transporter in 1998. ABCG2 physiologically acts as a part of a selfdefence mechanism for the organism; it enhances eliminating of toxic xenobiotic substances and harmful agents in the intestine, as well as through the blood-brain barrier and placenta. ABCG2 recognizes and transports numerous anticancer drugs including conventional chemotherapeutic and new targeted small therapeutic molecules in clinical usage. Development of ABCG2 inhibitors for clinical usage may allow increased penetration of therapeutic agents into sanctuary sites and increases their intestinal absorption. Here we review the mechanisms that modulate MDR mediated by the ABC transporter ABCG2 in normal and cancer cells by different levels including, epigenetic modifications, transcriptional, post-transcriptional, translation and post-translational regulation. Some clinical applications of ABCG2 inhibitors are also explained.
乳腺癌耐药蛋白（BCRP、ABCP或MXR）/ATP结合盒亚家族G成员2（ABCG2）于1998年被鉴定为一种多药耐药外排转运蛋白。ABCG2在生理上作为机体自我防御机制的一部分发挥作用；它增强了肠道以及通过血脑屏障和胎盘对有毒外源性物质和有害物质的清除。ABCG2识别并转运多种抗癌药物，包括临床使用的传统化疗药物和新型靶向小分子治疗药物。开发用于临床的ABCG2抑制剂可能会使治疗药物增加进入庇护所部位的渗透率，并提高其肠道吸收。在此，我们综述了在正常细胞和癌细胞中通过不同水平（包括表观遗传修饰、转录、转录后、翻译和翻译后调控）调节由ABC转运蛋白ABCG2介导的多药耐药的机制。还解释了ABCG2抑制剂的一些临床应用。
