Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Urology and Nephrology Research Center, Beheshti University of Medical Sciences, Tehran, Iran.
Biochem Pharmacol. 2019 May;163:94-100. doi: 10.1016/j.bcp.2019.02.006. Epub 2019 Feb 7.
Cisplatin is a broadly prescribed anti-tumor agent for the treatment of diverse cancers. Therapy with cisplatin, however, is associated with various adverse effects including nephrotoxicity and ototoxicity. AMP kinase (AMPK), an evolutionarily conserved enzyme, functions as the fundamental regulator of energy homeostasis. While AMPK activation protects normal tissues against cisplatin-induced toxicities, its impact in cancer is context-dependent and there is no single, uniform role for AMPK. On one hand, some report that AMPK activation augments cisplatin-induced apoptosis in cancer, while on the other hand, few reports indicate that AMPK activation rescues cancer cells from the cytotoxicity induced by cisplatin. Here we review the most salient signaling pathways regulated by AMPK with an emphasis on their relation to cisplatin toxicity and yet discuss context-dependent functions of AMPK in cancer.
顺铂是一种广泛应用于治疗多种癌症的抗肿瘤药物。然而，顺铂治疗与多种不良反应相关，包括肾毒性和耳毒性。AMP 激酶（AMPK）是一种进化上保守的酶，作为能量平衡的基本调节剂。AMPK 的激活可保护正常组织免受顺铂诱导的毒性，但在癌症中的影响是上下文相关的，AMPK 没有单一、统一的作用。一方面，一些研究表明 AMPK 的激活增强了顺铂诱导的癌症细胞凋亡，另一方面，也有少数研究表明 AMPK 的激活可使癌细胞免受顺铂引起的细胞毒性。在这里，我们综述了 AMPK 调节的最显著的信号通路，并特别强调它们与顺铂毒性的关系，同时还讨论了 AMPK 在癌症中的上下文相关功能。
