探索组蛋白去乙酰化酶抑制剂在癌症发展中的作用和治疗潜力。

IF 2 4区 医学 Q3 PHYSIOLOGY Journal of Physiology and Pharmacology Pub Date : 2024-04-01 Epub Date: 2024-05-06 DOI:10.26402/jpp.2024.2.01
C Zhang, H X Li, Y Man, Z H Jiang, P Yin, K Yu
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引用次数: 0

摘要

组蛋白在细胞核内的乙酰化和去乙酰化过程处于动态平衡状态。组蛋白乙酰转移酶(HATs)和组蛋白去乙酰化酶(HDACs)相互协作,精确调控正常的基因转录和表达。组蛋白乙酰转移酶/组蛋白去乙酰化酶的任何活性失调都会导致基因表达失控,进而导致肿瘤发生。组蛋白去乙酰化酶抑制剂(HDACIs)能够阻断细胞周期,从而抑制肿瘤细胞增殖和肿瘤生长。此外,HDACIs 还能显著降低 Bcl-2 和 B 细胞淋巴瘤超大型(Bcl-xL)等凋亡蛋白抑制剂的表达,同时上调 Bax、Bad 和 Bim 等促凋亡蛋白。此外,HDACIs 还能抑制肿瘤细胞的血管生成。作为一种新型靶向抗癌疗法,HDACIs 具有恢复肿瘤抑制基因表达、诱导细胞凋亡和刺激细胞分化的能力。此外,它们通过体内和体外的不同途径发挥抗癌作用,因此在肿瘤治疗方面前景广阔。本综述将深入探讨 HDACs 在癌症病理学中的参与作用,以及 HDACIs 作为新兴药物在癌症治疗中的治疗潜力。
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Exploring the role of histone deacetylase inhibitors in cancer development and therapeutic potential.

The process of acetylation and deacetylation of histones within the nucleus operates within a dynamic equilibrium. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) collaboratively and precisely regulate normal gene transcription and expression. Any disorder in the activity of HATs/HDACs can lead to uncontrolled gene expression, consequently resulting in tumorigenesis. Histone deacetylase inhibitors (HDACIs) have the capacity to block the cell cycle, thereby restraining tumor cell proliferation and tumor growth. Also, HDACIs exhibit a significant capability to diminish the expression of apoptosis protein inhibitors such as Bcl-2 and B-cell lymphoma-extra-large (Bcl-xL), while concurrently up-regulating pro-apoptotic proteins such as Bax, Bad, and Bim. Also, HDACIs demonstrate the ability to inhibit tumor cell angiogenesis. Representing a new category of targeted anti-cancer therapeutics, HDACIs possess the capability to restore the expression of tumor suppressor genes, induce apoptosis, and stimulate cell differentiation. Additionally, they exert anti-cancer effects through diverse pathways both in vivo and in vitro, thereby presenting promising prospects in tumor therapy. This review delves into the involvement of HDACs in cancer pathology and the therapeutic potential of HDACIs as emerging drugs in cancer treatment.

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来源期刊
CiteScore
4.00
自引率
22.70%
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0
审稿时长
6-12 weeks
期刊介绍: Journal of Physiology and Pharmacology publishes papers which fall within the range of basic and applied physiology, pathophysiology and pharmacology. The papers should illustrate new physiological or pharmacological mechanisms at the level of the cell membrane, single cells, tissues or organs. Clinical studies, that are of fundamental importance and have a direct bearing on the pathophysiology will also be considered. Letters related to articles published in The Journal with topics of general professional interest are welcome.
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