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他汀类药物调节自噬的治疗潜力及其影响

Implications on the Therapeutic Potential of Statins Modulation of Autophagy.

机构信息

Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Oxid Med Cell Longev. 2021 Jul 30;2021:9599608. doi: 10.1155/2021/9599608. eCollection 2021.

Abstract

Statins, which are functionally known as 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) inhibitors, are lipid-lowering compounds widely prescribed in patients with cardiovascular diseases (CVD). Several biological and therapeutic functions have been attributed to statins, including neuroprotection, antioxidation, anti-inflammation, and anticancer effects. Pharmacological characteristics of statins have been attributed to their involvement in the modulation of several cellular signaling pathways. Over the past few years, the therapeutic role of statins has partially been attributed to the induction of autophagy, which is critical in maintaining cellular homeostasis and accounts for the removal of unfavorable cells or specific organelles within cells. Dysregulated mechanisms of the autophagy pathway have been attributed to the etiopathogenesis of various disorders, including neurodegenerative disorders, malignancies, infections, and even aging. Autophagy functions as a double-edged sword during tumor metastasis. On the one hand, it plays a role in inhibiting metastasis through restricting necrosis of tumor cells, suppressing the infiltration of the inflammatory cell to the tumor niche, and generating the release of mediators that induce potent immune responses against tumor cells. On the other hand, autophagy has also been associated with promoting tumor metastasis. Several anticancer medications which are aimed at inducing autophagy in the tumor cells are related to statins. This review article discusses the implications of statins in the induction of autophagy and, hence, the treatment of various disorders.

摘要

他汀类药物,又称 3-羟基-3-甲基戊二酰辅酶 A(HMG-CoA)抑制剂,是广泛用于心血管疾病(CVD)患者的降脂药物。他汀类药物具有多种生物学和治疗功能,包括神经保护、抗氧化、抗炎和抗癌作用。他汀类药物的药理学特性归因于它们参与调节多种细胞信号通路。在过去的几年中,他汀类药物的治疗作用部分归因于自噬的诱导,自噬对于维持细胞内环境稳定至关重要,负责清除不利细胞或细胞内特定细胞器。自噬途径的失调机制与各种疾病的发病机制有关,包括神经退行性疾病、恶性肿瘤、感染,甚至衰老。自噬在肿瘤转移过程中是一把双刃剑。一方面,它通过限制肿瘤细胞坏死、抑制炎症细胞浸润肿瘤微环境以及产生释放诱导对肿瘤细胞产生强烈免疫反应的介质来抑制转移。另一方面,自噬也与促进肿瘤转移有关。几种旨在诱导肿瘤细胞自噬的抗癌药物与他汀类药物有关。本文综述了他汀类药物在诱导自噬以及治疗各种疾病中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d300/8349293/0f52eda0bf34/OMCL2021-9599608.001.jpg

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