Weifuchun suppresses the malignancy of gastric cancer cells by targeting KPNA2 through miR-26a-5p-mediated destabilization and the deactivation of the MAPK signaling pathway

Abstract

Ethnopharmacological relevanceWeifuchun (WFC) is a Traditional Chinese Medicine commonly used for treating atrophic gastritis and intestinal metaplasia. Till date, its antitumor effect on gastric cancer (GC) and the underlying mechanisms of the effect remains unelucidated. Aim of the studyWe aim to investigate if WFC can suppress the malignancy of stomach cancer cells and dissect the molecular basis and the associated molecular and cellular features. Materials and methodsStomach cancer cell lines and normal gastric epithelial cells were treated with WFC. CCK8 assay, caspase-3 activity assay, adhesion assay, microRNA database analysis, transfection, RT-PCR, Western Blotting, signaling pathway analysis, and in vivo GC model were employed to examine the changes in the features of the gastric cancer cells and the molecular mechanisms of the effect of WFC. ResultsHere we present data demonstrating that WFC suppresses the malignant cellular phenotypes of GC and this inhibitory effect is mediated by downregulating the expression of oncogenic KPNA2. Furthermore, WFC downregulates KPNA2 through miR-26a-5p-mediated gene silencing and the deactivated phosphorylation dynamics of mitogen-activated protein kinase (MAPK). The suppressive effect of WFC on stomach cancer cell behavior was further confirmed in animal model. ConclusionTherefore, WFC can exert inhibitory effect on the malignancy of GC cells by reducing the levels of KPNA2. Moreover, the miR-26a-5p rescue and the deactivation MAPK pathway induced by WFC result in the downregulation of KPNA2 expression. Thus, our findings suggest WFC as a potential treatment option against GC.