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降低胆固醇药物对Akt信号通路在预防肿瘤发生中的作用

Cholesterol-Lowering Drugs on Akt Signaling for Prevention of Tumorigenesis.

作者信息

Kumar Navneet, Mandal Chandi C

机构信息

Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, India.

Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Ajmer, India.

出版信息

Front Genet. 2021 Sep 16;12:724149. doi: 10.3389/fgene.2021.724149. eCollection 2021.

Abstract

Cholesterol has been reported to be accumulated in cancer cells. The metabolic dysregulation of the cholesterol is associated with tumor development and progression. The cholesterol-lowering drugs have been found to be involved in the prevention and treatment of various cancers. Akt, a serine/threonine kinase, can modulate the role of several downstream proteins involved in cell proliferation, migration, invasion, metabolism, and apoptosis. Since its involvement in several signaling pathways, its dysregulation is commonly reported in several cancers. Thus, targeting Akt could be an effective approach for cancer prevention and therapy. Cholesterol-lowering drugs have been found to affect the expression of Akt, and its activation in the cancer cells and thus have shown anticancer activity in different type of cancers. These drugs act on various signaling pathways such as PTEN/Akt, PI3k/Akt, Akt/NF-κB, Akt/FOXO1, Akt/mTOR, etc., which will be discussed in this article. This review article will discuss the significance of cholesterol in cancer cells, cholesterol-lowering drugs, the role of Akt in cancer cells, and the effects of cholesterol-lowering drugs on Akt in the prevention of therapy resistance and metastasis.

摘要

据报道,胆固醇会在癌细胞中蓄积。胆固醇的代谢失调与肿瘤的发生和发展有关。已发现降胆固醇药物参与多种癌症的预防和治疗。Akt是一种丝氨酸/苏氨酸激酶,可调节几种参与细胞增殖、迁移、侵袭、代谢和凋亡的下游蛋白的作用。由于其参与多种信号通路,在多种癌症中普遍报道其失调。因此,靶向Akt可能是癌症预防和治疗的有效方法。已发现降胆固醇药物会影响Akt的表达及其在癌细胞中的激活,从而在不同类型的癌症中显示出抗癌活性。这些药物作用于多种信号通路,如PTEN/Akt、PI3k/Akt、Akt/NF-κB、Akt/FOXO1、Akt/mTOR等,本文将对此进行讨论。这篇综述文章将讨论胆固醇在癌细胞中的意义、降胆固醇药物、Akt在癌细胞中的作用以及降胆固醇药物对Akt在预防治疗耐药性和转移方面的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a20/8483559/c0fc37a55587/fgene-12-724149-g001.jpg

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