Invasion and metastasis are the major causes leading to the high mortality of colon cancer. Ginsenoside Rg3 (Rg3), as a bioactive ginseng compound, is suggested to possess antimetastasis effects in colon cancer. However, the underlying molecular mechanisms remain unclear. In this study, we reported that Rg3 could effectively inhibit colon cancer cell invasion and metastasis through in vivo and in vitro studies. In addition, Rg3 suppressed the epithelial-mesenchymal transition (EMT) of HCT15 cells and SW48 cells evidenced by detecting EMT related markers E-cadherin, vimentin, and snail expression. Furthermore, inhibition of Notch signaling by LY411,575 or specific Hes1 siRNA obviously repressed colon cancer cell migration and metastasis, and induced increase in E-cadherin and decrease in vimentin and snail. Meanwhile, the expression of NICD and Hes1 was obviously decreased in the presence of Rg3. However, Rg3 failed to suppress EMT in Hes1 overexpressed colon cancer cells. In particular, Rg3 significantly reversed IL-6-induced EMT promotion and blocked IL-6- induced NICD and Hes1 upregulations. Overall, these findings suggested that Rg3 could inhibit colon cancer migration and metastasis via suppressing Notch-Hes1-EMT signaling.
Keywords: Colon Cancer; EMT; Ginsenoside Rg3; Metastasis; Notch.