Sun Meng-Yao, Song Ya-Nan, Zhang Miao, Zhang Chun-Yan, Zhang Li-Jun, Zhang Hong
Department of Pharmaceutical Botany, School of Pharmacy, Second Military Medical University, Shanghai 200433, P.R. China.
Central Laboratory, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China.
Oncol Lett. 2019 Jan;17(1):965-973. doi: 10.3892/ol.2018.9701. Epub 2018 Nov 15.
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, , 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.
人参皂苷Rg3是一种天然存在的植物化学物质，在癌症的预防和治疗中发挥着重要作用。在本研究中，为了揭示Rg3在肝癌细胞转移中的分子机制，研究了Rg3对肝癌细胞的抗迁移和抗侵袭作用。结果表明，Rg3显著抑制了人肝癌细胞HepG2和MHCC-97L的细胞迁移和侵袭，以及BABL/c裸鼠体内HepG2和MHCC-97L肿瘤的生长。Rho GTPase激活蛋白9（ARHGAP9）在HepG2和MHCC-97L细胞中的蛋白表达均增加。敲低ARHGAP9后，Transwell和肿瘤发生试验结果显示，Rg3的抗迁移、抗侵袭和抗肿瘤生长作用显著受损。Rg3诱导的ARHGAP9蛋白表达增加受到明显抑制。所有结果表明，ARHGAP9蛋白可能是Rg3抗转移作用的重要调节因子。据我们所知，本研究首次报道Rg3通过上调ARHGAP9的蛋白表达有效抑制肝癌细胞的迁移和侵袭，这表明Rg3是一种新型的天然治疗剂和肝癌治疗的靶点。
