(Fedde ex H.Wolff) Pimenov & Kljuykov Extract Suppresses Proliferation of HepG2 Cells via the PTEN-PI3K-AKT Pathway Uncovered by Integrating Network Pharmacology and Experiments.

Previous studies have shown that (Fedde ex H.Wolff) Pimenov & Kljuykov extracts (HWEs) have antitumor activity, but their mechanism is still unclear. In this study, we first combined network pharmacology with experimental evaluation and applied a comprehensive strategy to explore and prove the therapeutic potential and potential mechanism of HWE. The mRNA expression profiles of PTEN, PIK3A, and AKT1 are from the Cancer Cell Line Encyclopedia (CCLE) of the Broad Institute. Our results showed that HWE has a good inhibition on HepG2 cells, and a slight inhibition on other cells. The results of the CCLE database showed that PTEN/PIK3A/AKT1 mRNA expression was up-regulated in HepG2 cells. Through further study, it was found that HWE increased the release of LDH, induced early and late apoptosis, and increased ROS levels in HepG2 cells. Western blot showed that HWE regulates the expression of mitochondrial apoptosis-related proteins. Meanwhile, the expression of PTEN was increased, and the expression of phosphorylated PI3K and Akt was down-regulated after HWE treatment. Our results show that HWE promotes HepG2 cell apoptosis via the PTEN-PI3K-Akt signaling pathway. This study is the first to report the potential role of HWE in the treatment of liver cancer.