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


ABSTRACT:

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.

SUBMITTER: Wang M 

PROVIDER: S-EPMC8798386 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Wang Min M   Liu Xiuheng X   Chen Zhiyuan Z   Chen Hui H   Tan Yifan Y  

Translational cancer research 20201001 10


<h4>Background</h4>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.<h4>Methods</h4>TNF-α, NF-κB-P65 and E-cadherin were detected in prostate cancer and benign prostatic hyperplasia  ...[more]

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