Saikosaponin‐b2 Regulates the Proliferation and Apoptosis of Liver Cancer Cells by Targeting the MACC1/c‐Met/Akt Signalling Pathway

Abstract

Saikosaponin‐b2 (SS‐b2), an active ingredient derived from the root of Radix Bupleuri, possesses antitumour, anti‐inflammatory, antioxidative and hepatoprotective properties. We investigated the inhibition of tumour proliferation by SS‐b2 and the underlying molecular mechanisms, including the MACC1/p‐c‐Met/p‐Akt pathway expression in HepG2 liver cancer cells and H22 tumour‐bearing mice. Animal experiments showed that SS‐b2 significantly decreased the levels of MACC1, p‐c‐MET and p‐Akt in tumour tissue transplanted with H22 liver cancer cells in mice, while it increased the expression of p‐BAD. The results also revealed a concentration‐dependent suppression of MACC1, p‐c‐Met and p‐Akt expression in the SS‐b2 treatment group compared with the control group. Additionally, the suppression of MACC1 activation by SS‐b2 resulted in a reduction in the viability and proliferation of HepG2 liver cancer cells, and this reduction was comparable to that by doxorubicin (DOX). This suggests that SS‐b2 has significant efficacy in liver cancer, comparable to DOX. Meanwhile, Annexin V‐FITC/PI staining and western blot analysis of cleaved caspase 9 and cleaved caspase 3 demonstrated that SS‐b2 induced apoptosis of HepG2 liver cancer cells. These findings provide experimental evidence suggesting that SS‐b2 is a promising anticancer agent for liver cancer.