18β-glycyrrhetinic acid inhibits hepatocellular carcinoma development by reversing hepatic stellate cell-mediated immunosuppression in mice

Int J Cancer. 2013 Apr 15;132(8):1831-41. doi: 10.1002/ijc.27852. Epub 2012 Oct 20.

Abstract

Hepatic stellate cells (HSCs) have immunosuppressive capabilities and contribute to the occurrence and development of hepatocellular carcinoma (HCC). Thus, activated HSCs may be a suitable target for HCC therapy. Our study used mixed leukocyte reactions (MLR) in vitro to demonstrate that 18β-glycyrrhetinic acid (GA) could reverse HSC-mediated immunosuppression by reducing T-cell apoptosis and regulatory T (Treg) cells expression, thereby enhancing the ability of T cells to attack tumor cells and attenuating HCC cell invasiveness. Moreover, we established a HCC orthotopic implantation model in immunocompetent C57BL/6 mice, which suggested that GA played a protective role in HCC development by reducing immunosuppression mediated by HSCs in the tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Flow Cytometry
  • Glycyrrhetinic Acid / analogs & derivatives*
  • Glycyrrhetinic Acid / pharmacology
  • Hepatic Stellate Cells / immunology*
  • Liver Neoplasms, Experimental / immunology
  • Liver Neoplasms, Experimental / prevention & control*
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • T-Lymphocytes / immunology

Substances

  • 18alpha-glycyrrhetinic acid
  • Glycyrrhetinic Acid