Insights into the inhibition of stomach cancer MKN45 cell growth by Poria cocos ethanol-soluble extract based on MAPK/PI3K signaling pathways and components cell fishing

Abstract

Ethnopharmacological relevancePoria cocos F.A. Wolf is an edible fungus with forming sclerotia, which has the effects of promoting diuresis, exuding dampness, invigorating the spleen, and regulating the stomach. P. cocos has a high application in the clinic of traditional Chinese medicine, and some studies have indicated that P. cocos has a good effect on tumor diseases. According to ancient records and modern studies, P. cocos wine offers beneficial effects in terms of strengthening tendons and bones and anti-tumor effects. Aim of the studyTo understand the substance composition of P. cocos ethanol-soluble extract (PESE) and then further study the effect and potential mechanism of PESE components on gastric cancer. Materials and methodsIn vitro and in vivo experiments were performed to detect the cell activity and apoptotic condition. Differential expression analysis and pathway enrichment were performed based on transcriptomics and were verified by real-time polymerase chain reaction and western blotting. The mice of the stomach cancer tumor model were randomly categorized into three groups. The weight and tumor volume of the mice were measured, and the pathological characteristics of tumor tissue and immunohistochemical changes were determined. Then, the main active components of PESE were detected by MKN45 cell fishing. ResultsIn vitro experiments showed that PESE inhibited the proliferation of MKN45 cells, but it did not induce apoptosis. Based on the transcriptome and western blotting results, the inhibition of MKN45 proliferation by PESE may be influenced by mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase–protein kinase B (PI3K-Akt) signaling pathways. In vivo experiments showed that PESE inhibited tumor growth in mice and caused partial necrosis of tumor cells but had no toxic effect on mice. Cell fishing identified nine triterpenoids of P. cocos as the major active components of PESE. ConclusionsThe results indicated that PESE has a significant inhibitory effect on stomach cancer, and its mechanism probably commonly affects the MAPK and PI3K-Akt signaling pathways, which could be due to the triterpenoid components.