动物模型与人类重大疾病机理重点实验室知识库

Taraxasterol has potent anti-inflammatory and anti-tumor activity. However, the effect and potential mechanisms of Taraxasterolon the growth of human liver cancer have not been clarified. Histidine triad nucleotide-binding protein 1 (Hint1) is a tumorsuppressor and its downregulated expression is associated with the development of cancer. Here, we report that Taraxasteroltreatment significantly suppressed cell proliferation and induced cell cycle arrest at G0/G1 phase and apoptosis in liver cancercells, but not in non-tumor hepatocytes. Furthermore, Taraxasterol upregulated Hint1 and Bax, but downregulated Bcl2 andcyclin D1 expression, accompanied by promoting the demethylation in the Hint1 promoter region in liver cancer cells. Theeffects of Taraxasterol were abrogated by Hint1 silencing and partially mitigated by Bax silencing, Bcl2 or cyclin D1 over-expressioninHepG2cells.Moreover,oraladministrationwithTaraxasteroldidnotaffectbodyweight,urinaryproteinlevels,andthe heart, liver, and kidney morphology in BALB/c mice but effectively inhibited the growth of implanted SK-Hep1 tumor invivo. Collectively, we demonstrate that Taraxasterol inhibits the growth of liver cancer at least partially by enhancing Hint1expression to regulate Bax, Bcl2, and cyclin D1 expression. Taraxasterol may be a drug candidate for the treatment of humanliver cancer.