journal contribution
posted on 2023-03-31, 03:05 authored by Jianjiang Xie, Jianheng Ye, Zhiduan Cai, Yong Luo, Xuejin Zhu, Yulin Deng, Yuanfa Feng, Yingke Liang, Ren Liu, Zhaodong Han, Yuxiang Liang, Yu Zheng, Rujun Mo, Yangjia Zhuo, Yongding Wu, Funeng Jiang, Jianguo Zhu, Chin-Lee Wu, Weide Zhong <p>Figure S1 showed the expression of GPD1 and GPD2 in cells were determined by Western blot.</p>
Funding
National Natural Science Foundation of China
Guangzhou Municipal Science and Technology Project
Bureau of Health of Guangzhou Municipality
Fundamental Research Funds for the Central Universities
Natural Science Foundation of Guangdong Province
History
ARTICLE ABSTRACT
Metformin is an oral drug widely used for the treatment of type 2 diabetes mellitus. Numerous studies have demonstrated the value of metformin in cancer treatment. However, for metformin to elicit effects on cancer often requires a high dosage, and any underlying mechanism for how to improve its inhibitory effects remains unknown. Here, we found that low mRNA expression of glycerol-3-phosphate dehydrogenase 1 (GPD1) may predict a poor response to metformin treatment in 15 cancer cell lines. In vitro and in vivo, metformin treatment alone significantly suppressed cancer cell proliferation, a phenotype enhanced by GPD1 overexpression. Total cellular glycerol-3-phosphate concentration was significantly increased by the combination of GPD1 overexpression and metformin treatment, which suppressed cancer growth via inhibition of mitochondrial function. Eventually, increased reactive oxygen species and mitochondrial structural damage was observed in GPD1-overexpressing cell lines treated with metformin, which may contribute to cell death. In summary, this study demonstrates that GPD1 overexpression enhances the anticancer activity of metformin and that patients with increased GPD1 expression in tumor cells may respond better to metformin therapy.
GPD1 overexpression enhances the anticancer effect of metformin through synergistic inhibition of mitochondrial function, thereby providing new insight into metformin-mediated cancer therapy.
