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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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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
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author Wang, Min
Liu, Xiuheng
Chen, Zhiyuan
Chen, Hui
Tan, Yifan
author_facet Wang, Min
Liu, Xiuheng
Chen, Zhiyuan
Chen, Hui
Tan, Yifan
author_sort Wang, Min
collection PubMed
description 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.
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spelling pubmed-87983862022-02-02 Metformin suppressed tumor necrosis factor-α-induced epithelial-mesenchymal transition in prostate cancer by inactivating the NF-κB signaling pathway Wang, Min Liu, Xiuheng Chen, Zhiyuan Chen, Hui Tan, Yifan Transl Cancer Res Original Article 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. AME Publishing Company 2020-10 /pmc/articles/PMC8798386/ /pubmed/35117220 http://dx.doi.org/10.21037/tcr-20-1186 Text en 2020 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Original Article
Wang, Min
Liu, Xiuheng
Chen, Zhiyuan
Chen, Hui
Tan, Yifan
Metformin suppressed tumor necrosis factor-α-induced epithelial-mesenchymal transition in prostate cancer by inactivating the NF-κB signaling pathway
title Metformin suppressed tumor necrosis factor-α-induced epithelial-mesenchymal transition in prostate cancer by inactivating the NF-κB signaling pathway
title_full Metformin suppressed tumor necrosis factor-α-induced epithelial-mesenchymal transition in prostate cancer by inactivating the NF-κB signaling pathway
title_fullStr Metformin suppressed tumor necrosis factor-α-induced epithelial-mesenchymal transition in prostate cancer by inactivating the NF-κB signaling pathway
title_full_unstemmed Metformin suppressed tumor necrosis factor-α-induced epithelial-mesenchymal transition in prostate cancer by inactivating the NF-κB signaling pathway
title_short Metformin suppressed tumor necrosis factor-α-induced epithelial-mesenchymal transition in prostate cancer by inactivating the NF-κB signaling pathway
title_sort metformin suppressed tumor necrosis factor-α-induced epithelial-mesenchymal transition in prostate cancer by inactivating the nf-κb signaling pathway
topic Original Article
url 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
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