Network pharmacology approach and experimental verification of salidroside in the treatment of hepatocellular carcinoma

Abstract

Abstract Background Salidroside (Sal) is a bioactive component extracted from the rhizome of Rhodiola rosea L. Pharmacological studies have shown that Sal has good anti-cancer properties in various cancers, but the exact mechanism is not clear. Method This study validated the efficacy and explored the potential mechanisms of Sal in treating hepatocellular carcinoma (HCC) by integrating network pharmacology analyses and experimental verification. The pharmacological effects and molecular mechanism of Sal on HCC were explored by network pharmacology approach. HepG2 cells were treated with Sal and/or chloroquine diphosphate (CQ). The cell counting kit-8 (CCK-8) assay, inverted microscope (IM) observation, transmission electron microscope (TEM) observation, various staining were used to detect the condition of autophagy and apoptosis, and the western blotting was used to detect related proteins. Moreover, Sal and/or CQ was also used to treat HCC mice, the hematoxylin and eosin (H & E) staining was used to observe the pathological change of tumor tissue, the immunohistochemistry and western blotting were used to detect the change of related proteins in tumor tissue. Results The network pharmacology approach successfully identified that Sal might adjust autophagy flux through PI3K/AKT/mTOR pathway, which might affect the occurrence and development of HCC. The in vitro experiments indicated that Sal induced HepG2 cells autophagy and apoptosis. The in vitro and vivo experiments indicated that inhibition of autophagy promoted mitochondrial damage and apoptosis induced by Sal. Moreover, Caspase cascade reactions might be involved in these processes, especially the increased expression of cleaved-caspase-3 and cleaved-caspase-9. Notably, Sal also inhibited the activation of PI3K/AKT/mTOR pathway, while CQ promoted the activation of this pathway. Conclusion These findings provide important view for the molecular mechanism of interaction between autophagy and apoptosis, and also provide new insights for monitoring, diagnosis and treatment of HCC.