Metformin inhibits epithelial‑mesenchymal transition of oral squamous cell carcinoma via the mTOR/HIF‑1&alpha;/PKM2/STAT3 pathway

Yin,Weihuang; Liu,Yang; Liu,Xinchen; Ma,Xiaozhou; Sun,Bin; Yu,Ziying

doi:10.3892/ol.2020.12292

Metformin inhibits epithelial‑mesenchymal transition of oral squamous cell carcinoma via the mTOR/HIF‑1α/PKM2/STAT3 pathway

Authors:
- Weihuang Yin
- Yang Liu
- Xinchen Liu
- Xiaozhou Ma
- Bin Sun
- Ziying Yu
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Affiliations: Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Endodontics, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: November 11, 2020 https://doi.org/10.3892/ol.2020.12292
Article Number: 31
Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epithelial‑mesenchymal transition (EMT) serves an important role in the formation and development of various types of cancer, including oral squamous cell carcinoma (OSCC). Metformin, used for treating type 2 diabetes, has been revealed to exert an anticancer effect in various types of cancer, including liver, breast and colorectal cancer. However, its role in the EMT of OSCC has been rarely reported. Therefore, the present study aimed to investigate the effects of metformin on EMT and to identify its underlying mechanism in OSCC. Firstly, EMT was induced in CAL‑27 cells using CoCl₂. Subsequently, the effects of metformin on cell viability, migration and xenograft growth were evaluated in vitro and in vivo. Reverse transcription‑quantitative PCR was performed to detect the expression levels of E‑cadherin, vimentin, snail family transcriptional repressor 1, mTOR, hypoxia inducible factor 1α, pyruvate kinase M2 and STAT3. The results demonstrated that metformin abolished CoCl2‑induced cell proliferation, migration, invasion and EMT. Moreover, metformin reversed EMT in OSCC by inhibiting the mTOR‑associated HIF‑1α/PKM2/STAT3 signaling pathway. Overall, the present findings characterized a novel mechanism via which metformin modulated EMT in OSCC.

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