Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 132, Issue 8, Pages 1831-1841Publisher
WILEY
DOI: 10.1002/ijc.27852
Keywords
hepatic stellate cells; 18-glycyrrhetinic acid; immunoregulation; hepatocellular carcinoma; T cells
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Funding
- National Key Sci-Tech Special Project of China [2012ZX10002-011-005]
- National Natural Science Foundation of China [81171976, 81201894]
- Natural Science Foundation of Fujian Province, China [2011D003]
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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 18-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.
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