Poricoic Acid A, an Active Ingredient Extracted From Poria cocos, Inhibits Lung Cancer Cell Growth by Suppressing MEK/ERK Signaling Pathway

ABSTRACT Lung cancer continues to be a significant clinical challenge, highlighting the urgent need for effective therapeutic strategies to improve patient outcomes. Poricoic acid A (PAA), an active compound derived from the traditional Chinese medicinal mushroom Poria cocos (Fuling), has gained attention for its potential antitumor effects. Although prior studies have suggested its efficacy in vitro, the therapeutic potential, mechanism of action, and safety of PAA in inhibiting cancer growth have yet to be thoroughly investigated. The aim of this study was to explore the therapeutic potential of PAA against lung cancer through comprehensive in vitro and in vivo experiments. In vitro, H460 and H1299 lung cancer cells were treated with PAA to evaluate its impact on cell growth, apoptosis, and the cell cycle using CCK‐8 assay, colony formation assay, and flow cytometry analyses. In vivo, mouse models were used to assess both the efficacy of PAA in inhibiting tumor growth and its safety across primary organs. PAA significantly inhibited the growth of lung cancer cells, induced apoptosis, and caused cell cycle arrest in the G 2 /M phase. Mechanistic investigations revealed that PAA directly targeted MEK1/2, resulting in the downregulation of the MEK/ERK signaling pathway and subsequent suppression of cell growth and proliferation. In mouse models, PAA exhibited low toxicity and minimal adverse effects on primary organs. PAA holds promise as a potential therapeutic agent for lung cancer, providing a solid foundation for future clinical investigation.