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

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...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2018-10, Vol.13 (10), p.e0205449-e0205449
Main Authors: Kang, Sanghee, Kim, Bo Ram, Kang, Myoung-Hee, Kim, Dae-Young, Lee, Dae-Hee, Oh, Sang Cheul, Min, Byung Wook, Um, Jun Won
Format: Article
Language:English
Subjects:
Adenocarcinoma
Angiogenesis
Anticancer properties
Antidiabetics
Antitumor activity
Biology and Life Sciences
Breast cancer
Cancer
Cell cycle
Cell growth
Cell survival
Chemotherapy
Colon
Colon cancer
Colorectal cancer
Colorectal carcinoma
Cytokines
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Gene expression
Genomes
Growth factors
Hospitals
Insulin resistance
Interleukin 6
Kinases
Medicine
Medicine and Health Sciences
Mesenchyme
Metastases
Metastasis
Metformin
Mortality
Oncology
Patients
Predictions
Prostate
Proteins
Signal transduction
Signaling
Surgery
Survival analysis
TOR protein
Tumor cell lines
Tumorigenesis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0205449