Omipalisib Inhibits Esophageal Cancer Growth through PI3K/AKT/mTOR Signalling Pathway Disruption

Esophageal squamous cell carcinoma (OSCC) is a lethal digestive tract malignancy with limited effective interventions. This study aims to explore a new potential inhibitor on OSCC and investigate the underlying mechanisms. Based on a drug screen of an FDA-proven library consisting of 1404 compounds, we demonstrated that Omipalisib, a dual PI3K/mTOR inhibitor, markedly inhibited cell proliferation and colony formation in a panel of OSCC cell lines. Mechanistically, Omipalisib induced G0/G1 phase cell cycle arrest and apoptosis. Moreover, RNA-seq, KEGG and GSEA confirmed that the PI3K/mTOR signalling pathway is the primary target of Omipalisib in OSCC cells. Omipalisib treatment suppressed the PI3K/mTOR signalling pathway. Furthermore, Omipalisib exerted a significant antineoplastic effect on OSCC tumour xenografts in BALB/c nude mice without obvious side effects. The present study supports the rationale for using Omipalisib as a therapeutic approach for OSCC cases and suggests the potential clinical evaluation of this strategy. Overall design: In this study, we investigated the therapeutic effects and underlying mechanisms of Omipalisib in OSCC cells based on a screen of compound library.