Department of Gastroenteroloy and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan.
Curr Pharm Des. 2017;23(25):3629-3644. doi: 10.2174/0929867324666170713150440.
AMP-activated protein kinase (AMPK) is a protein kinase that maintains homeostasis in cells and organs. As a master regulator of metabolism, AMPK coordinates many metabolic reactions. AMPK is a key factor in diabetes and metabolic syndrome associated with dysregulation of the metabolic status. Recently, AMPK has also attracted attention as a tumor suppressor. The aim of this article is to discuss about the role of AMPK in diabetes as well as cancer and to evaluate its effectiveness in treatment and prevention of these diseases.
We reviewed studies of signaling mechanism involving AMPK and research on the role of AMPK in human disease including diabetes and cancer. In particular, we focused our attention on clinical trials about cancer treatment and prevention targeting AMPK.
Many experimental studies reported the relation of AMPK and various metabolic reactions, mainly regulating energy homeostasis. Recent studies showed effect of AMPK on arrest of cell cycle as well as suppression of inflammation, which are important factors for carcinogenesis. Although some clinical studies investigated cancer treatment and prevention targeting AMPK, the effective yields in clinical trial have been limited.
AMPK activation as represented by metformin showed to improve disorders associated with diabetes and metabolic syndrome and became a well-established treatment strategy for these diseases. The increasing evidence suggests that AMPK is a promising target in the treatment and prevention of cancer. Further investigation including long-term clinical trials with large sample size is needed.
AMP 激活的蛋白激酶（AMPK）是一种在细胞和器官中维持内稳态的蛋白激酶。作为代谢的主调控因子，AMPK 协调许多代谢反应。AMPK 是与代谢状态失调相关的糖尿病和代谢综合征的关键因素。最近，AMPK 作为肿瘤抑制因子也引起了关注。本文旨在讨论 AMPK 在糖尿病和癌症中的作用，并评估其在这些疾病的治疗和预防中的有效性。
我们回顾了涉及 AMPK 的信号转导机制的研究以及关于 AMPK 在人类疾病（包括糖尿病和癌症）中的作用的研究。特别是，我们关注了针对 AMPK 的癌症治疗和预防的临床试验。
许多实验研究报告了 AMPK 与各种代谢反应的关系，主要是调节能量稳态。最近的研究表明，AMPK 对细胞周期停滞以及炎症抑制有作用，这是致癌的重要因素。尽管一些临床研究针对 AMPK 进行了癌症治疗和预防，但临床试验中的有效收益有限。
以二甲双胍为代表的 AMPK 激活已被证明可改善与糖尿病和代谢综合征相关的疾病，并成为这些疾病的既定治疗策略。越来越多的证据表明，AMPK 是癌症治疗和预防的有前途的靶点。需要进一步进行包括大样本量的长期临床试验的研究。
