Anti-metastatic effect of metformin via repression of interleukin 6-induced epithelial- mesenchymal transition in human colon cancer cells

Sanghee Kang, Bo Ram Kim, Myoung Hee Kang, Dae Young Kim, Dae Hee Lee, Sang Cheul Oh, Byung Wook Min, Jun Won Um

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Metformin, a first-line drug used to treat type 2 diabetes, has also been shown to have anticancer effects against a variety of malignancies, including colorectal cancer. Although inhibition of the mTOR pathway is known to be the most important mechanism for the antitumor effects of metformin, other mechanisms remain unclear. The purpose of this study was to identify the antitumor mechanism of metformin in colorectal cancer using high-throughput data, and then test the mechanism experimentally. We identified the gene signature of metformin- treated colon cancer cells. This signature was processed for prediction using colon adenocarcinoma patient data from the Cancer Genome Atlas to classify the patients showing a gene expression pattern similar to that in metformin-treated cells. This patient group showed better overall and disease-free survival. Furthermore, pathway analysis revealed that the metformin-predicted group was characterized by decreased interleukin (IL)-6 pathway signaling, epithelial-mesenchymal transition, and colon cancer metastatic signaling. We induced epithelial-mesenchymal transition in colon cancer cell lines via IL-6 treatment, which increased cell motility and promoted invasion. However, these effects were blocked by metformin. These findings suggest that blockade of IL-6-induced epithelial-mesenchymal transition is an antitumor mechanism of metformin.

Original languageEnglish
Article numbere0205449
JournalPLoS One
Volume13
Issue number10
DOIs
Publication statusPublished - 2018 Oct 1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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