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PLoS One. 2014 Apr 30;9(4):e95884. doi: 10.1371/journal.pone.0095884. eCollection 2014.

Metformin inhibits the IL-6-induced epithelial-mesenchymal transition and lung adenocarcinoma growth and metastasis.

Author information

  • 1Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China; Department of Oncology, Fuzhhou General Hospital of Nanjing Military Commond, Fuzhou, China.
  • 2Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
  • 3Department of Respiratory Medicine, Daping hospital, Third Military Medical University, Chongqing, China.
  • 4Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
  • 5Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China; Biomedical Analysis Center, Third Military Medical University, Chongqing, China.

Abstract

OBJECTIVE:

Epithelial-mesenchymal transition (EMT) plays an important role in cancer tumorigenesis. However, the underlying mechanisms of EMT in lung adenocarcinoma, and how this process might be inhibited, remain to be explored. This study investigated the role of IL-6 in lung adenocarcinoma cell EMT and explored the potential effects of metformin on this process.

METHODS:

Invasion assay and MTT assay was performed to determine cell invasion and cell proliferation. Western blotting, immunofluorescence, real-time PCR, ELISA, and immunohistochemistry were performed to detect the expression of IL-6, E-cadherin, Vimentin, and p-STAT3.

RESULTS:

We discovered that IL-6, via STAT3 phosphorylation, could promote lung adenocarcinoma cell invasion via EMT in vitro. This was supported by the inverse correlation between E-cadherin and IL-6 expression, positive correlation between IL-6 and vimentin mRNA expression and between STAT3 phosphorylation and IL-6 expression in tumor tissues. Importantly, metformin inhibited tumor growth and distant metastases in tumor-bearing nude mice and reversed IL-6-induced EMT both in vitro and in vivo. Furthermore, we found that blockade of STAT3 phosphorylation might be the underlying mechanism of metformin inhibition of IL-6-induced EMT.

CONCLUSIONS:

Collectively, our present results show that enhanced IL-6 expression, via STAT3 phosphorylation, is a mechanism of EMT in lung adenocarcinoma. We found that metformin could inhibit IL-6-induced EMT possibly by blocking STAT3 phosphorylation.

PMID:
24789104
[PubMed - indexed for MEDLINE]
PMCID:
PMC4005743
Free PMC Article
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