METTL3 inhibitor STM2457 impairs tumor progression and enhances sensitivity to anlotinib in OSCC

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Oral squamous cell carcinoma (OSCC) remains a significant health challenge.
• METTL3 (methyltransferase-like 3) is implicated in various cancers, including OSCC.
• Targeting METTL3 and EGFR presents a potential therapeutic strategy for OSCC.

Purpose of the Study:

• To evaluate the efficacy of STM2457, a novel METTL3 inhibitor, as a monotherapy and in combination with anlotinib for OSCC treatment.
• To investigate the underlying molecular mechanisms of this combination therapy.
• To assess the impact on cancer stemness and epithelial-mesenchymal transition (EMT) in OSCC.

Main Methods:

• In vitro studies utilized OSCC cell lines with assays for cell viability (CCK8), migration, colony formation, sphere formation, cell cycle, and apoptosis.
• In vivo efficacy was assessed using nude mice tumor xenograft models.
• Molecular mechanisms were explored through western blotting, qRT-PCR, MeRIP-qPCR, immunofluorescence, and immunohistochemistry.

Main Results:

• The combination of STM2457 and anlotinib demonstrated enhanced inhibition of OSCC cell survival and proliferation, alongside increased apoptosis in vitro.
• This combination therapy significantly reduced cancer stemness properties and EMT features.
• In vivo studies confirmed the potent anti-tumor efficacy of the combined treatment.
• Mechanistically, the combination downregulated epidermal growth factor receptor (EGFR) expression in OSCC cells.

Conclusions:

• The combination of STM2457 and anlotinib targeting EGFR exhibits a multi-faceted anti-tumor effect in OSCC.
• This therapeutic strategy holds promise for future clinical applications in OSCC treatment.
• Further research may elucidate the full potential of anlotinib and STM2457 combination therapy for OSCC.