Metformin promotes apoptosis in hepatocellular carcinoma through the CEBPD-induced autophagy pathway.
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| Abstract |
Metformin, as an AMP-activated protein kinase (AMPK) activator, can activate autophagy. A study showed that metformin decreased the risk of hepatocellular carcinoma (HCC) in diabetic patients. However, the detailed mechanism in the metformin-mediated anticancer effect remains an open question. Transcription factor CCAAT/enhancer-binding protein delta (CEBPD) has been suggested to serve as a tumor suppressor and is responsive to multiple anticancer drugs in HCC. In this study, we found that CEBPD and autophagy are involved in metformin-induced cell apoptosis in Huh7 cells. The underlying mechanisms in this process included a reduction in Src-mediated CEBPD protein degradation and an increase in CEBPD-regulated LC3B and ATG3 gene transcription under metformin treatment. We also found that AMPK is involved in metformin-induced CEBPD expression. Combined treatment with metformin and rapamycin can enhance autophagic cell death through the AMPK-dependent and AMPK-independent pathway, respectively. Taken together, we provide a new insight and therapeutic approach by targeting autophagy in the treatment of HCC.
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| Authors | Hsin-Hwa Tsai, Hong-Yue Lai, Yueh-Chiu Chen, Chien-Feng Li, Huei-Sheng Huang, Hsiao-Sheng Liu, Yau-Sheng Tsai, Ju-Ming Wang |
| Journal | Oncotarget (Oncotarget) Vol. 8 Issue 8 Pg. 13832-13845 (Feb 21 2017) ISSN: 1949-2553 [Electronic] United States |
| PMID | 28099155 (Publication Type: Journal Article) |
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