Metformin suppressed tumor necrosis factor-α-induced epithelial-mesenchymal transition in prostate cancer by inactivating the NF-κB signaling pathway

Background: Epithelial-mesenchymal transition (EMT) and the tumor micro- environment are involved in tumorigenesis and progression. Tumor necrosis factor-a (TNF-alpha) is a proinflammatory cytokine in cancer that might be associated with promoting cancer invasion and metastasis. This study aimed to explore the potential effects of metformin on TNF-alpha-induced EMT in prostate cancer. Methods: TNF-alpha, NF-kappa B-P65 and E-cadherin were detected in prostate cancer and benign prostatic hyperplasia (BPH) tissues by immunohistochemistry. Prostate cancer PC3 cells were treated with TNF-alpha with or without metformin. Then, the cell invasion and cell proliferation ability was separately determined by scratch assay and invasion assay. The expression of E-cadherin, N-cadherin, Vimentin, TNF-alpha, NF-kappa B-P65, p-IKK and p-I kappa B alpha were detected by western blotting and immunofluorescence. Results: TNF-alpha and NF-kappa B-P65 were positively related to higher Gleason scores, but E-cadherin was negatively related to higher Gleason scores. TNF-alpha significantly increased the migration and invasion ability of prostate cancer cells, and it significantly promoted the expression of N-cadherin, Vimentin, NF-kappa B-P65, p-IKK and p-I kappa B alpha but reduced the expression of E-cadherin. Metformin significantly inhibited TNF-alpha-induced migration and invasion of prostate cancer cells. Furthermore, metformin decreased TNF-alpha-induced expression of N-cadherin, Vimentin, NF-kappa B-P65, p-IKK and p-I kappa B alpha but increased the expression of E-cadherin. Moreover, metformin inhibited NF-kappa B-P65 translocation into the nucleus. Conclusions: TNF-alpha accelerated the EMT process potentially via activation of the NF-kappa B signaling pathway. Metformin might suppress TNF-alpha-induced EMT in prostate cancer by inactivating the NF-kappa B signaling pathway.