Metformin induces apoptosis by microRNA-26a-mediated downregulation of myeloid cell leukaemia-1 in human oral cancer cells

Wang,Fang; Xu,Jincheng; Liu,Hao; Liu,Zhe; Xia,Fei

doi:10.3892/mmr.2016.5143

Metformin induces apoptosis by microRNA-26a-mediated downregulation of myeloid cell leukaemia-1 in human oral cancer cells

Authors:
- Fang Wang
- Jincheng Xu
- Hao Liu
- Zhe Liu
- Fei Xia
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Affiliations: Department of Oncology, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China, Department of Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233000, P.R. China, Department of Biochemical Pharmacology, Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China
Published online on: April 15, 2016 https://doi.org/10.3892/mmr.2016.5143
Pages: 4671-4676

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Abstract

In recent years, population-based studies and retrospective analyses of clinical studies have shown that metformin treatment is associated with reduced cancer incidence and a decrease in cancer‑associated mortality. However, its mechanism of action remains to be fully understood. The present study demonstrates the effects of metformin on KB human oral cancer cells and explores the role of myeloid cell leukaemia‑1 (Mcl‑1) in metformin‑induced mitochondria‑dependent cellular apoptosis. It was demonstrated that metformin exposure caused significant suppression of KB cell proliferation and induced cell death. Furthermore, metformin induced apoptosis through the downregulation of Mcl‑1 in KB human oral cancer cells, and the overexpression of Mcl‑1 in metformin‑treated KB cells significantly increased cell viability. Consistently, Bax and Bim were upregulated in metformin‑treated cells. The results also reveal that microRNA (miR)‑26a expression was markedly increased by metformin. Subsequent to enforced miR‑26a expression in KB cells using miR‑26a mimics, cell viability and the level of Mcl‑1 decreased. These results suggest that the anti‑proliferative effects of metformin in KB cells may result partly from induction of apoptosis by miR-26a-induced downregulation of Mcl-1.

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