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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-α (TNF-α) is a proinflammatory cytokine in cancer that might be associated with promoting cancer invasion and metastasis. This study aimed to expl...

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Detalles Bibliográficos
Autores principales: Wang, Min, Liu, Xiuheng, Chen, Zhiyuan, Chen, Hui, Tan, Yifan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798386/
https://www.ncbi.nlm.nih.gov/pubmed/35117220
http://dx.doi.org/10.21037/tcr-20-1186
Descripción
Sumario:BACKGROUND: Epithelial-mesenchymal transition (EMT) and the tumor micro- environment are involved in tumorigenesis and progression. Tumor necrosis factor-α (TNF-α) 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-α-induced EMT in prostate cancer. METHODS: TNF-α, NF-κB-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-α 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-α, NF-κB-P65, p-IKK and p-IκBα were detected by western blotting and immunofluorescence. RESULTS: TNF-α and NF-κB-P65 were positively related to higher Gleason scores, but E-cadherin was negatively related to higher Gleason scores. TNF-α significantly increased the migration and invasion ability of prostate cancer cells, and it significantly promoted the expression of N-cadherin, Vimentin, NF-κB-P65, p-IKK and p-IκBα but reduced the expression of E-cadherin. Metformin significantly inhibited TNF-α-induced migration and invasion of prostate cancer cells. Furthermore, metformin decreased TNF-α-induced expression of N-cadherin, Vimentin, NF-κB-P65, p-IKK and p-IκBα but increased the expression of E-cadherin. Moreover, metformin inhibited NF-κB-P65 translocation into the nucleus. CONCLUSIONS: TNF-α accelerated the EMT process potentially via activation of the NF-κB signaling pathway. Metformin might suppress TNF-α-induced EMT in prostate cancer by inactivating the NF-κB signaling pathway.