Integrating network pharmacology and experimental validation reveals PI3K/AKT as a critical pathway in pachymic acid-induced inhibition of hepatocellular carcinoma

Abstract

Pachymic acid (PA), a natural lanost-8-ene-type triterpenoid isolated from Poria cocos , exhibits diverse pharma cological activities, including anti-oxidant, anti-inflammatory, antiaging, and hypnotic effects. Emerging evi dence has highlighted its potential anticancer properties, particularly its ability to suppress the proliferation of various cancer cell lines, though the underlying mechanisms remain largely undefined. In this study, we employed a network pharmacology approach to explore the anti-hepatocellular carcinoma (anti-HCC) effects of PA. GO and KEGG enrichment analyses identified the PI3K/AKT signalling pathway as a key candidate mediating PA’s activity in liver cancer cells. This prediction was subsequently validated by Western blotting, which confirmed that PA markedly inhibited the growth of HepG2 HCC cells through suppression of the PI3K/AKT pathway, as evidenced by reduced AKT phosphorylation. Collectively, our findings provide new insights into the anticancer mechanisms of PA and support its potential as a promising candidate for novel anti-HCC therapies.