Tanshinol inhibits the growth, migration and invasion of hepatocellular carcinoma cells via regulating the PI3K-AKT signaling pathway.

BACKGROUND

Tanshinol is an active constituent of Salvia miltiorrhiza and possess anti-inflammatory, antioxidant, and anti-bacterial activity. Herein, we explored the role of tanshinol on the growth and aggressiveness of hepatocellular carcinoma (HCC) cells in vitro and in vivo.

MATERIALS AND

METHODS

The proliferation of a panel of HCC cell lines was measured using MTT assay. The expressions of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT) were detected by immunofluorescence staining and immunohistochemical assay. The levels of Bcl-2 and Bax were determined using immunoblotting assay. The secretions of matrix metalloproteinase-2 (MMP-2) and MMP-9 were detected by ELISA. The migration and invasion abilities of HepG2 cell were determined using wound healing and Transwell invasion assays. The apoptosis of HepG2 cell induced by tanshinol was analyzed by Annexin V/propidium iodide staining. A xenograft model was constructed to investigate the inhibitory effect of tanshinol on HepG2 cell growth in vivo. To further investigate the role of tanshinol on the metastasis of HepG2 cell in vivo, an experimental metastasis assay was performed.

RESULTS

Tanshinol inhibited the growth and colony formation of HCC cell in vitro. Tanshinol also induced the apoptosis of HepG2 cell and inhibited the migration and invasion of HepG2 cell. In in vivo experiments, tanshinol suppressed the tumor growth and metastasis of HepG2 cell. Furthermore, the phosphorylation of PI3K and AKT was decreased by tanshinol in vitro and in vivo.

CONCLUSION

Tanshinol exerts its anti-cancer effects via regulating the PI3K-AKT signaling pathway in HCC.