Bimiralisib suppresses proliferation and migration of gastric cancer cells via PI3K/mTOR pathway inhibition

Gastric cancer remains a leading cause of cancer-related mortality worldwide, underscoring the need for effective targeted therapeutic strategies. The phosphatidylinositol 3-kinase (PI3K)/mechanistic target of rapamycin (mTOR) signaling pathway is frequently dysregulated in gastric cancer and represents a promising therapeutic target. However, its clinical applicability remains insufficiently explored. Therefore, this study aimed to identify actionable therapeutic targets and evaluate the potential of a clinically relevant PI3K/mTOR inhibitor, bimiralisib, in gastric cancer. Analysis of The Cancer Genome Atlas dataset revealed elevated expression of PIK3CA and mTOR in gastric cancer tissues. Small-molecule inhibitor screening identified bimiralisib as a potent suppressor of gastric cancer cell viability. Functional assays demonstrated that bimiralisib significantly inhibited cell proliferation, clonogenic growth, spheroid formation, and migration, and induced G1 phase arrest with a reduction in the S phase population. Mechanistically, bimiralisib reduced phosphorylation of AKT and mTOR, confirming effective inhibition of PI3K/mTOR signaling. Consistently, PIK3CA knockdown recapitulated these effects. In addition, bimiralisib treatment was associated with upregulation of E2F4, suggesting a link between pathway inhibition and cell cycle regulation. Collectively, these findings demonstrate that targeting PI3K/mTOR signaling with bimiralisib suppresses gastric cancer cell growth and migration, supporting its potential as a targeted therapeutic strategy.