Peng Ting, Gong Jun, Jin Yongzhe, Zhou Yanping, Tong Rongsheng, Wei Xin, Bai Lan, Shi Jianyou
Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, Chengdu, 610072, China.
Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, Chengdu, 610072, China.
Eur J Med Chem. 2018 Apr 25;150:742-756. doi: 10.1016/j.ejmech.2018.03.046. Epub 2018 Mar 16.
Phosphodiesterases (PDEs) are a class of enzymes that hydrolyze cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) which is involved in many physiological processes including visual transduction, cell proliferation and differentiation, cell-cycle regulation, gene expression, inflammation, apoptosis, and metabolic function. PDEs are composed of 11 different families and each family contains different subtypes. The distribution, expression, regulation mode and sensitivity to inhibitors of each subtype are different, and they are involved in cancer, inflammation, asthma, depression, erectile dysfunction and other pathological processes of development. A large number of studies have shown that PDEs play an important role in the development of tumors by affecting the intracellular level of cAMP and/or cGMP and PDEs could become diagnostic markers or therapeutic targets. This review will give a brief overview of the expression and regulation of PDE families in the process of tumorigenesis and their anti-tumor inhibitors, which may guide the design of novel therapeutic drugs targeting PDEs for anticancer agent.
磷酸二酯酶（PDEs）是一类能够水解环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）的酶，它们参与许多生理过程，包括视觉传导、细胞增殖与分化、细胞周期调控、基因表达、炎症、细胞凋亡和代谢功能。PDEs由11个不同的家族组成，每个家族包含不同的亚型。各亚型的分布、表达、调控方式及对抑制剂的敏感性均有所不同，它们参与癌症、炎症、哮喘、抑郁、勃起功能障碍等病理过程的发展。大量研究表明，PDEs通过影响细胞内cAMP和/或cGMP水平在肿瘤发生发展中发挥重要作用，并且PDEs有望成为诊断标志物或治疗靶点。本文综述将简要概述PDE家族在肿瘤发生过程中的表达与调控及其抗肿瘤抑制剂，这可能为设计新型靶向PDEs的抗癌治疗药物提供指导。
