Open AccessAntitumor effects of metformin are a result of inhibiting nuclear factor kappa B nuclear translocation in esophageal squamous cell carcinoma
Author(s) -
Sekino Nobufumi,
Kano Masayuki,
Matsumoto Yasunori,
Sakata Haruhito,
Akutsu Yasunori,
Hanari Naoyuki,
Murakami Kentaro,
Toyozumi Takeshi,
Takahashi Masahiko,
Otsuka Ryota,
Yokoyama Masaya,
Shiraishi Tadashi,
Okada Koichiro,
Hoshino Isamu,
Iida Keiko,
Akimoto Aki Komatsu,
Matsubara Hisahiro
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13523
Subject(s) - metformin , medicine , epithelial–mesenchymal transition , cancer research , motility , apoptosis , cancer , inflammation , cell growth , pharmacology , endocrinology , diabetes mellitus , biology , metastasis , microbiology and biotechnology , biochemistry , genetics
Esophageal squamous cell carcinoma ( ESCC ) is an intractable digestive organ cancer that has proven difficult to treat despite multidisciplinary therapy, and a new treatment strategy is demanded. Metformin is used for type 2 diabetes mellitus and its antitumor effects have been reported recently. Metformin exerts antitumor effects in various respects, such as inhibiting inflammation, tumor growth and epithelial‐mesenchymal transition ( EMT ). However, few reports have described the efficacy of metformin on ESCC , and their findings have been controversial. We analyzed the antitumor effects of metformin and clarified its effects on anti‐inflammation, growth suppression and EMT inhibition. Activation of nuclear factor kappa B ( NF ‐κB), the major transcription factor induced by inflammation, was investigated by immunostaining. We found that localization of NF ‐κB in the nucleus was reduced after metformin treatment. This suggests that metformin inhibited the activation of NF ‐κB. Metformin inhibited tumor growth and induced apoptosis in ESCC cell lines. Associated with EMT , we examined cell motility by a wound healing assay and the epithelial marker E‐cadherin expression of various ESCC cell lines by western blotting. Metformin inhibited cell motility and induced E‐cadherin expression. In conclusion, metformin showed multiple antitumor effects such as growth suppression, invasion inhibition, and control of EMT by inhibiting NF ‐κB localization on ESCC . Further exploration of the marker of treatment efficacy and combination therapy could result in the possibility for novel treatment to use metformin on ESCC .