Zeng Chen-Ming, Chang Lin-Lin, Ying Mei-Dan, Cao Ji, He Qiao-Jun, Zhu Hong, Yang Bo
Zhejiang Province Key Laboratory of Anti-cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University Hangzhou, China.
Front Pharmacol. 2017 Mar 14;8:119. doi: 10.3389/fphar.2017.00119. eCollection 2017.
Aldo-keto reductases comprise of AKR1C1-AKR1C4, four enzymes that catalyze NADPH dependent reductions and have been implicated in biosynthesis, intermediary metabolism, and detoxification. Recent studies have provided evidences of strong correlation between the expression levels of these family members and the malignant transformation as well as the resistance to cancer therapy. Mechanistically, most studies focus on the catalytic-dependent function of AKR1C isoforms, like their impeccable roles in prostate cancer, breast cancer, and drug resistance due to the broad substrates specificity. However, accumulating clues showed that catalytic-independent functions also played critical roles in regulating biological events. This review summarizes the catalytic-dependent and -independent roles of AKR1Cs, as well as the small molecule inhibitors targeting these family members.
醛酮还原酶由AKR1C1 - AKR1C4组成，这四种酶催化依赖NADPH的还原反应，并参与生物合成、中间代谢和解毒过程。最近的研究提供了证据，表明这些家族成员的表达水平与恶性转化以及癌症治疗耐药性之间存在强烈关联。从机制上讲，大多数研究集中在AKR1C亚型的催化依赖性功能上，比如它们在前列腺癌、乳腺癌以及由于广泛底物特异性导致的耐药性中所起的无可挑剔的作用。然而，越来越多的线索表明，催化非依赖性功能在调节生物学事件中也起着关键作用。本综述总结了AKR1C的催化依赖性和非依赖性作用，以及靶向这些家族成员的小分子抑制剂。
