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靶向癌症中的胆固醇代谢:从分子机制到治疗意义。

Targeting cholesterol metabolism in Cancer: From molecular mechanisms to therapeutic implications.

机构信息

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.

出版信息

Biochem Pharmacol. 2023 Dec;218:115907. doi: 10.1016/j.bcp.2023.115907. Epub 2023 Nov 4.

Abstract

Cholesterol is an essential component of cell membranes and helps to maintain their structure and function. Abnormal cholesterol metabolism has been linked to the development and progression of tumors. Changes in cholesterol metabolism triggered by internal or external stimuli can promote tumor growth. During metastasis, tumor cells require large amounts of cholesterol to support their growth and colonization of new organs. Recent research has shown that cholesterol metabolism is reprogrammed during tumor development, and this can also affect the anti-tumor activity of immune cells in the surrounding environment. However, identifying the specific targets in cholesterol metabolism that regulate cancer progression and the tumor microenvironment is still a challenge. Additionally, exploring the potential of combining statin drugs with other therapies for different types of cancer could be a worthwhile avenue for future drug development. In this review, we focus on the molecular mechanisms of cholesterol and its derivatives in cell metabolism and the tumor microenvironment, and discuss specific targets and relevant therapeutic agents that inhibit aspects of cholesterol homeostasis.

摘要

胆固醇是细胞膜的重要组成部分,有助于维持其结构和功能。异常的胆固醇代谢与肿瘤的发生和发展有关。内部或外部刺激引发的胆固醇代谢变化可促进肿瘤生长。在转移过程中,肿瘤细胞需要大量的胆固醇来支持其在新器官中的生长和定植。最近的研究表明,胆固醇代谢在肿瘤发生过程中被重新编程,这也会影响周围环境中免疫细胞的抗肿瘤活性。然而,确定调节癌症进展和肿瘤微环境的胆固醇代谢中的特定靶点仍然是一个挑战。此外,探索将他汀类药物与其他疗法结合用于治疗不同类型癌症的潜力可能是未来药物开发的一个有价值的途径。在这篇综述中,我们重点讨论了胆固醇及其衍生物在细胞代谢和肿瘤微环境中的分子机制,并讨论了抑制胆固醇动态平衡特定靶点和相关治疗剂。

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