School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, P.R. China.
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, P.R. China.
Int J Oncol. 2020 Nov;57(5):1103-1115. doi: 10.3892/ijo.2020.5124. Epub 2020 Sep 22.
Cancer represents a severe challenge to healthcare systems and individuals worldwide. The development of multiple drug resistance is a major issue regarding cancer therapy, which can result in the progression of disease. Cholesterol is a major constituent of cell membranes and participates in the regulation of several cellular processes, such as cell growth, proliferation, differentiation, survival and apoptosis. Numerous studies have provided correlative support for a role of cholesterol in cancer development and drug resistance. In the present review, recent insights into the regulation of cholesterol metabolism, the association between cholesterol and the efficacy of antitumor agents in preclinical studies, as well as the possible mechanisms through which cholesterol influences drug resistance, are summarized. Furthermore, the clinical relevance of cholesterol to the development of cancer, as well as strategies targeting cholesterol for therapeutic intervention are detailed. Collectively, studies on various types of cancer have suggested that increased cholesterol levels promote resistance to chemotherapeutic drugs in cancer through a variety of mechanisms, and that the depletion of cholesterol using statins significantly enhances the sensitivity of the therapeutic agents. However, additional studies are required to enhance the current understanding of the involvement of cholesterol in the development of drug‑resistant cancer.
癌症是对全球医疗体系和个人的严重挑战。多药耐药性的发展是癌症治疗的一个主要问题，它可能导致疾病的进展。胆固醇是细胞膜的主要成分之一，参与调节细胞生长、增殖、分化、存活和凋亡等多种细胞过程。大量研究为胆固醇在癌症发展和耐药性中的作用提供了相关性支持。在本综述中，总结了胆固醇代谢调节的最新见解、胆固醇与临床前研究中抗肿瘤药物疗效之间的关联，以及胆固醇影响耐药性的可能机制。此外，还详细阐述了胆固醇与癌症发展的临床相关性，以及针对胆固醇的治疗干预策略。总之，对各种类型癌症的研究表明，胆固醇水平升高通过多种机制促进了癌症对化疗药物的耐药性，而使用他汀类药物消耗胆固醇可显著提高治疗药物的敏感性。然而，需要进一步的研究来增强目前对胆固醇在耐药性癌症发展中的作用的理解。
