Ginsenoside Rg3 inhibits the migration and invasion of liver cancer cells by increasing the protein expression of ARHGAP9

Ginsenoside Rg3, a naturally occurring phytochemical, serves an important role in the prevention and treatment of cancer. In the present study, with the aim to reveal the molecular mechanism of Rg3 in liver cancer cell metastasis, the anti-migration and anti-invasion effects of Rg3 on liver cancer cells were investigated. It was demonstrated that Rg3 caused marked inhibition of cell migration and invasion of human liver cancer cells, HepG2 and MHCC-97L, in vitro, and the growth of HepG2 and MHCC-97L tumors in BABL/c nude mice. The protein expression of Rho GTPase activating protein 9 (ARHGAP9) was increased both in HepG2 and MHCC-97L cells. Following ARHGAP9 knockdown, the results of Transwell and tumorigenesis assays revealed that the anti-migration, anti-invasion and anti-tumor growth effects of Rg3 were impaired significantly. The increased expression of ARHGAP9 protein induced by Rg3 was remarkably suppressed. All results suggested that ARHGAP9 protein may be a vital regulator in the anti-metastatic role of Rg3. To the best of our knowledge, the present study is the first to report that Rg3 effectively suppressed the migration and invasion of liver cancer cells by upregulating the protein expression of ARHGAP9, indicating a novel natural therapeutic agent and a therapeutic target for the treatment of liver cancer.