Research Papers:

Metformin increases chemo-sensitivity via gene downregulation encoding DNA replication proteins in 5-Fu resistant colorectal cancer cells

Sung-Hee Kim, Soon-Chan Kim and Ja-Lok Ku _

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Oncotarget. 2017; 8:56546-56557. https://doi.org/10.18632/oncotarget.17798

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Sung-Hee Kim1, Soon-Chan Kim2 and Ja-Lok Ku1,2

1Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea

2Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea

Correspondence to:

Ja-Lok Ku, email: [email protected]

Keywords: colorectal cancer, 5-Fu resistant-cell line, metformin, cancer stem cell (CSC), DNA replication

Received: January 17, 2017     Accepted: April 27, 2017     Published: May 11, 2017


Metformin is most widely prescribed for type 2 diabetes. Recently, evidences have shown that metformin has anticancer effects on pancreatic-, colorectal-, ovarian-, and other cancers. Because metformin has less adverse effects and is inexpensive, it could be a useful chemo-therapeutic agent with anticancer effects. In this study, we demonstrated metformin inhibited by cell proliferation, cell migration ability, clonogenic ability, and cancer stem cell population. Metformin also induced cell cycle arrest in parental-(SNU-C5), and 5-Fu resistant-colorectal cancer cell line (SNU-C5_5FuR). Moreover, a treatment that combines 5-Fu and metformin was found to have a synergistic effect on the cell proliferation rate, especially in SNU-C5_5FuR, which was mediated by the activation of AMPK pathway and NF-ƙB pathway, well-known metformin mechanisms. In this study, we suggested novel anticancer mechanism of metformin that inhibited DNA replication machinery, such as the MCM family in SNU-C5_5FuR. In conclusion, we provided that how metformin acts as not only a chemo-sensitizer, but also as a synergistic effector of 5-Fu in the 5-Fu resistant-cell line. We speculate that metformin used for adjuvant therapy is effective on 5-Fu resistant cancer cells.

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