Ruanjian Sanjie Decoction Induces Apoptosis in Triple-negative Breast Cancer Cells by Downregulating cIAP1/2 and XIAP

Abstract

Background: Traditional Chinese medicine (TCM) comprises a unique theoretical system developed over thousands of years. The previous study reported that Ruanjian Sanjie (RJSJ) exerts anti-tumor effects by inducing cell apoptosis. However, the mechanism is not clear. Methods: In this study, we investigated the possible mechanism by the strategy of combining network pharmacology analysis with experiment (in vitro and in vivo). First, four kinds of breast cancer cell lines were used to conduct proliferation, apoptosis and cell cycle analysis. Secondly, to study pathophysiological processes of breast cancer at the molecular network level, we for the first time constructed an “integrated apoptosis module network of breast cancer” by assembling the regulatory relationships of canonical apoptosis signaling pathways. Through the strategy of combining network analysis and experiments, we analyzed the main mechanism of RJSJ in breast cancer and screened out the core genes. We further studied the inhibitory effect of RJSJ combined with carboplatin (CBP) in vivo. Finally, the synergistic effect of RJSJ and CBP were analyzed and the potential active components in RJSJ were predicted.Results: This study demonstrated that RJSJ could significantly inhibit breast cancer cell proliferation and induce apoptosis in a concentration-dependent manner. The primary mechanism of RJSJ in the treatment of breast cancer was pro-apoptotic. The core apoptosis genes regulated by RJSJ were cIAP1/2 and XIAP. We also found that RJSJ in combination with CBP tended to synergistically induce apoptosis, which might mainly be achieved through the regulation of multiple targets and pathways. Alexandrin (BX05, XKC02, SCG01), baicalin (BX22), guanosine (BX32), arjunglucoside I (XKC10) etc. were predicted as potential active components.Conclusions: These findings provide the rationale for exploring the therapeutic effects of RJSJ against breast cancer and providing a bridge for the combined use of Chinese and Western medicine.