Wang Fang, Xu Jincheng, Liu Hao, Liu Zhe, Xia Fei
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.
Mol Med Rep. 2016 Jun;13(6):4671-6. doi: 10.3892/mmr.2016.5143. Epub 2016 Apr 15.
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.
近年来，基于人群的研究以及临床研究的回顾性分析表明，二甲双胍治疗与癌症发病率降低及癌症相关死亡率下降有关。然而，其作用机制仍有待充分了解。本研究证明了二甲双胍对KB人舌癌细胞的影响，并探讨了髓样细胞白血病-1（Mcl-1）在二甲双胍诱导的线粒体依赖性细胞凋亡中的作用。结果表明，二甲双胍处理可显著抑制KB细胞增殖并诱导细胞死亡。此外，二甲双胍通过下调KB人舌癌细胞中的Mcl-1诱导细胞凋亡，而在二甲双胍处理的KB细胞中过表达Mcl-1可显著提高细胞活力。同样，在二甲双胍处理的细胞中Bax和Bim上调。结果还显示，二甲双胍可显著增加微小RNA（miR）-26a的表达。使用miR-26a模拟物在KB细胞中强制表达miR-26a后，细胞活力和Mcl-1水平降低。这些结果表明，二甲双胍对KB细胞的抗增殖作用可能部分源于miR-26a诱导的Mcl-1下调所引发的细胞凋亡。
