Affiliation:
1. Department of Oral and Maxillofacial Surgery The First Affiliated Hospital of Sun Yat‐Sen University Guangzhou China
2. College & Hospital of Stomatology Guangxi Medical University Nanning China
3. Center for Translational Medicine, Institute of Precision Medicine The First Affiliated Hospital of Sun Yat‐Sen University Guangzhou China
4. Clinical Research Center Affiliated Hospital of Guangdong Medical University Zhanjiang China
5. Division of Pulmonary and Critical Care Medicine The First Affiliated Hospital of Sun Yat‐Sen University Guangzhou China
6. Laboratory of General Surgery The First Affiliated Hospital of Sun Yat‐Sen University Guangzhou China
7. Hospital of Stomatology The First Affiliated Hospital of Jinan University Guangzhou China
Abstract
AbstractObjectivesTo investigate the inhibitory effects of STM2457, which is a novel METTL3 (m6A writer) inhibitor, both as a monotherapy and in combination with anlotinib, in the treatment of oral squamous cell carcinoma (OSCC) both in vitro and in vivo.Materials and MethodsThe efficacy of STM2457 or STM2457 plus anlotinib was evaluated using two OSCC cell lines by CCK8, transwell, colony formation, would‐healing, sphere formation, cell cycle, apoptosis assays, and nude mice tumor xenograft techniques. The molecular mechanism study was carried out by western blotting, qRT‐PCR, MeRIP‐qPCR, immunofluorescence, and immunohistochemistry.ResultsSTM2457 combined with anlotinib enhanced inhibition of cellular survival/proliferation and promotion of apoptosis in vitro. Moreover, this combinatorial approach exerted a notable reduction in stemness properties and EMT (epithelial‐mesenchymal transition) features of OSCC cells. Remarkably, in vivo studies validated the efficacy of the combination treatment. Mechanistically, our investigations revealed that the combined action of STM2457 and anlotinib exerted downregulatory effects on EGFR (epidermal growth factor receptor) expression in OSCC cells.ConclusionsThe combination of STM2457 and anlotinib targeting EGFR exerted a multiple anti‐tumor effect. In near future, anlotinib combined with STM2457 may provide a novel insight for the treatment of OSCC.
Funder
National Natural Science Foundation of China