Researchers from Sichuan University and the Chinese Academy of Medical Sciences and Peking Union Medical College evaluated the bioactive compound ginsenoside Rg3, a component of ginseng, and its potential against hepatocellular carcinoma (HCC). Their study was published in The American Journal of Chinese Medicine.
- The sodium-hydrogen exchanger 1 (NHE1) plays a key role in the growth and development of HCC. It is a promising target for the treatment of HCC.
- Ginsenoside Rg3 is said to have pleiotropic antitumor effects on HCC but the mechanisms behind its suppression of HCC remain unclear.
- The researchers discovered that Rg3 exerts its effect on HCC by decreasing NHE1 expression.
- They found that epidermal growth factor (EGF) significantly increases NHE1 expression. EGF also increases the phosphorylated extracellular signal-regulated protein kinase (ERK1/2) level and hypoxia-inducible factor 1 alpha (HIF-1a) expression.
- ERK1/2-specific inhibitor PD98059 blocked EGF-stimulated HIF-1 alpha and NHE1 expression.
- Meanwhile, HIF-1a-specific inhibitor 2-methoxyestradiol (2-MeOE2) blocked EGF-stimulated NHE1 expression.
- From the results of in vivoand in vitro studies, the researchers reported that treatment with Rg3 decreased the expression of EGF, EGF receptor (EGFR), phosphorylated ERK1/2, and HIF-1a.
- They also found that RG3 can decrease EGF-stimulated NHE1 expression by inhibiting the EGF-EGFR-ERK1/2-HIF-1a signal axis in HCC.
From these results, the researchers concluded that Rg3 is an effective multi-target anti-tumor agent against HCC.
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Li X, Tsauo J, Geng C, Zhao H, Lei X, Li X. GINSENOSIDE RG3 DECREASES NHE1 EXPRESSION VIA INHIBITING EGF-EGFR-ERK1/2-HIF-1? PATHWAY IN HEPATOCELLULAR CARCINOMA: A NOVEL ANTITUMOR MECHANISM. The American Journal of Chinese Medicine. 2018;46(08):1915–1931. DOI: 10.1142/s0192415x18500969