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• W3096032403 endingPage "104971" @default.
• W3096032403 startingPage "104971" @default.
• W3096032403 abstract "We aimed to explore the effects of metformin on oral squamous cell carcinoma (OSCC) cell proliferation and the associated molecular mechanisms. We established an OSCC model in SCC15 cells overexpressing nerve growth factor receptor (NGFR) or the N-terminal region (aa 1–250; NGFR-N), and assessed cell proliferation by CCK-8 assay, colony formation assay, and cell cycle analysis. Levels of NGFR and related genes and proteins were detected by qPCR and western blotting, and NGFR and NGFR-N affinity for p53 was assessed by immunoprecipitation assay. Additionally, the effects of NGFR and NGFR-N on p53 binding with its downstream gene promoters were analyzed by chromatin immunoprecipitation. Metformin inhibited OSCC cell proliferation and blocked NGFR proteolysis, thereby reducing the generation of its intracellular domain and NGFR-N. Moreover, compared with NGFR, NGFR-N showed higher affinity for p53 and more strongly inactivated p53 to promote cell proliferation. Furthermore, upregulation of NGFR-N downregulated levels of p53-specific downstream transcripts and proteins, whereas these levels were significantly upregulated in metformin-treated cells overexpressing NGFR. These results showed that metformin inhibited cell proliferation by suppressing NGFR proteolysis, thereby promoting its antitumor effect in OSCC and offering novel insight into a role for metformin in OSCC treatment." @default.
• W3096032403 created "2020-11-09" @default.
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• W3096032403 date "2021-01-01" @default.
• W3096032403 modified "2023-10-10" @default.
• W3096032403 title "Metformin inhibits proliferation of oral squamous cell carcinoma cells by suppressing proteolysis of nerve growth factor receptor" @default.
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• W3096032403 doi "https://doi.org/10.1016/j.archoralbio.2020.104971" @default.
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