Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
Oncol Rep. 2021 Mar;45(3):1249-1260. doi: 10.3892/or.2020.7909. Epub 2020 Dec 24.
Metformin is an antidiabetic drug that has been reported to have an inhibitory effect on different types of cancers, including oral squamous cell carcinoma (OSCC). However, few studies have explored the role of Yes‑associated protein (YAP), a vital factor contributing to OSCC biology, in metformin‑induced anticancer activity in OSCC cells. Thus, the purpose of the present study was to investigate the molecular relationship between metformin and YAP in OSCC cells. CAL27 and SCC25 cell lines were treated with various concentrations of metformin for 24 h. Cell proliferation was detected by Cell Counting Kit‑8 (CCK‑8) and flow cytometric assays. Cell apoptosis was analyzed using flow cytometry. The intracellular protein levels of target genes were determined by western blotting. It was demonstrated that metformin affected the cell cycle and apoptosis of CAL27 and SCC25 cells. Alteration of YAP protein expression affected metformin‑mediated changes in the cell cycle and apoptosis of CAL27 and SCC25 cells. In addition, compared to the control treatment, metformin treatment decreased the protein levels of YAP, mTOR, p‑mTOR and c‑Myc. The overexpression of YAP alleviated the inhibitory effect of metformin on the protein expression of mTOR, p‑mTOR and c‑Myc. The combination of metformin and verteporfin markedly enhanced the effects of metformin on the protein expression of mTOR, p‑mTOR and c‑Myc. Therefore, the results of the present study suggest that metformin suppresses OSCC by inhibiting YAP protein expression and by suppressing the YAP‑mediated effects of metformin on the protein expression of mTOR and c‑Myc.
二甲双胍是一种抗糖尿病药物，据报道它对包括口腔鳞状细胞癌（OSCC）在内的多种癌症具有抑制作用。然而，很少有研究探讨 Yes 相关蛋白（YAP）在二甲双胍诱导的 OSCC 细胞抗癌活性中的作用，YAP 是促进 OSCC 生物学的重要因素。因此，本研究旨在探讨二甲双胍和 YAP 在 OSCC 细胞中的分子关系。用不同浓度的二甲双胍处理 CAL27 和 SCC25 细胞系 24 小时。用细胞计数试剂盒（CCK-8）和流式细胞术检测细胞增殖。用流式细胞术分析细胞凋亡。用 Western blot 测定靶基因的细胞内蛋白水平。结果表明，二甲双胍影响 CAL27 和 SCC25 细胞的细胞周期和凋亡。YAP 蛋白表达的改变影响了二甲双胍对 CAL27 和 SCC25 细胞周期和凋亡的调节作用。此外，与对照组相比，二甲双胍处理降低了 YAP、mTOR、p-mTOR 和 c-Myc 的蛋白水平。YAP 的过表达减轻了二甲双胍对 mTOR、p-mTOR 和 c-Myc 蛋白表达的抑制作用。二甲双胍和维替泊芬联合使用显著增强了二甲双胍对 mTOR、p-mTOR 和 c-Myc 蛋白表达的抑制作用。因此，本研究结果表明，二甲双胍通过抑制 YAP 蛋白表达和抑制 YAP 介导的二甲双胍对 mTOR 和 c-Myc 蛋白表达的作用来抑制 OSCC。
