Zhang Xuemei, Shi Lei, Lu Xiaona, Zheng Wenlan, Shi Jia, Yu Shihan, Feng Hai, Yu Zhuo
Department of Hepatopathy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Department of Clinical Laboratory, Shuguang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai 201203, China.
Pharmaceuticals (Basel). 2024 Aug 30;17(9):1142. doi: 10.3390/ph17091142.
Hepatocellular carcinoma (HCC) is a highly aggressive liver malignancy and one of the most lethal cancers globally, with limited effective therapeutic options. Bile acids (BAs), as primary metabolites of hepatic cholesterol, undergo enterohepatic circulation involving secretion into the intestine and reabsorption into the liver, and their composition is modulated in this process. Recent clinical observations have revealed a correlation between alteration in the BAs profile and HCC incidence, and the effect of various species of BAs on HCC development has been investigated. The regulatory effect of different BA species on cell proliferation, migration, and apoptosis in tumor cells, as well as their interaction with gut microbiota, inflammation, and immunity have been identified to be involved in HCC progression. In this review, we summarize the current understanding of the diverse functions of BAs in HCC pathogenesis and therapy, from elucidating the fundamental mechanisms underlying both tumor-promoting and tumor-suppressive consequences of various BA species to exploring potential strategies for leveraging BAs for HCC therapy. We also discuss ongoing efforts to target specific BA species in HCC treatment while highlighting new frontiers in BA biology that may inspire further exploration regarding their connection to HCC.
肝细胞癌（HCC）是一种侵袭性很强的肝脏恶性肿瘤，也是全球最致命的癌症之一，有效的治疗选择有限。胆汁酸（BAs）作为肝脏胆固醇的主要代谢产物，参与肠肝循环，包括分泌到肠道和重新吸收到肝脏，其组成在此过程中受到调节。最近的临床观察揭示了胆汁酸谱改变与肝细胞癌发病率之间的相关性，并且已经研究了各种胆汁酸对肝细胞癌发展的影响。已确定不同种类的胆汁酸对肿瘤细胞中细胞增殖、迁移和凋亡的调节作用，以及它们与肠道微生物群、炎症和免疫的相互作用与肝细胞癌进展有关。在这篇综述中，我们总结了目前对胆汁酸在肝细胞癌发病机制和治疗中多种功能的理解，从阐明各种胆汁酸促肿瘤和抑肿瘤后果的基本机制到探索利用胆汁酸进行肝细胞癌治疗的潜在策略。我们还讨论了在肝细胞癌治疗中针对特定胆汁酸种类的 ongoing efforts，同时强调胆汁酸生物学的新前沿领域，这些领域可能会激发对其与肝细胞癌联系的进一步探索。
