The anti-tumor effects of Metformin are due to inhibiting NF-κB nuclear translocation in esophageal squamous cell carcinoma

Summary

Esophageal squamous cell carcinoma (ESCC) is an intractable digestive organ cancer that has proven difficult to treat despite multidisciplinary therapy, and the 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. The activation of NF-κB, the major transcription factor induced by inflammation was investigated by immunostaining. We found that the 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 the cell motility by a wound healing assay and the epithelial marker E-cadherin expression of various ESCC cell lines by Western blotting. Metformin inhibited the cell motility and induced E-cadherin expression. In conclusion, metformin showed multiple antitumor effects such as growth suppression, invasion inhibition, and to control EMT by inhibiting NF-κB localization on ESCC. Further exploration on the marker of treatment efficacy and combinatory therapy could bring out the possibility for novel treatment to use metformin on ESCC.

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from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nEtANw