Hepatocellular carcinoma: Novel understandings and therapeutic strategies based on bile acids (Review)

Int J Oncol. 2022 Oct;61(4):117. doi: 10.3892/ijo.2022.5407. Epub 2022 Aug 5.

Abstract

Bile acids (BAs) are the major components of bile and products of cholesterol metabolism. Cholesterol is catalyzed by a variety of enzymes in the liver to form primary BAs, which are excreted into the intestine with bile, and secondary BAs are formed under the modification of the gut microbiota. Most of the BAs return to the liver via the portal vein, completing the process of enterohepatic circulation. BAs have an important role in the development of hepatocellular carcinoma (HCC), which may participate in the progression of HCC by recognizing receptors such as farnesoid X receptor (FXR) and mediating multiple downstream pathways. Certain BAs, such as ursodeoxycholic acid and obeticholic acid, were indicated to be able to delay liver injury and HCC progression. In the present review, the structure and function of BAs were introduced and the metabolism of BAs and the process of enterohepatic circulation were outlined. Furthermore, the mechanisms by which BAs participate in the development of HCC were summarized and possible strategies for targeting BAs and key sites of their metabolic processes to treat HCC were suggested.

Keywords: bile acid; enterohepatic circulation; farnesoid x receptor; hepatocellular carcinoma; obeticholic acid; ursodeoxycholic acid.

Publication types

  • Review

MeSH terms

  • Bile Acids and Salts / metabolism
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / metabolism
  • Cholesterol / metabolism
  • Enterohepatic Circulation / physiology
  • Humans
  • Liver / metabolism
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / metabolism

Substances

  • Bile Acids and Salts
  • Cholesterol

Grants and funding

This work was supported by a grant from the Natural Science Foundation of Guangxi (grant no. 2021GXNSFAA325001) and a grant from the Shenyang Science and Technology Plan Fund Project (grant no. 20-205-4-094).