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

METTL3 抑制剂 STM2457 可抑制 OSCC 的肿瘤进展并增强对安罗替尼的敏感性

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作者:Lianlian Liu, Tingting Zhao, Siyi Zheng, Dongxiao Tang, Hui Han, Chunlong Yang, Xin Zheng, Juan Wang, Jieyi Ma, Wei Wei, Zhaoyu Wang, Shuqi He, Qianting He

Conclusions

The 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.

Methods

The 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.

Results

STM2457 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. Conclusions: The 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.

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