PMID- 35117220
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220501
IS  - 2219-6803 (Electronic)
IS  - 2218-676X (Print)
IS  - 2218-676X (Linking)
VI  - 9
IP  - 10
DP  - 2020 Oct
TI  - Metformin suppressed tumor necrosis factor-alpha-induced epithelial-mesenchymal 
      transition in prostate cancer by inactivating the NF-kappaB signaling pathway.
PG  - 6086-6095
LID - 10.21037/tcr-20-1186 [doi]
AB  - BACKGROUND: Epithelial-mesenchymal transition (EMT) and the tumor micro- 
      environment are involved in tumorigenesis and progression. Tumor necrosis 
      factor-alpha (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-kappaB-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-kappaB-P65, p-IKK and p-IkappaBalpha were detected by western blotting and 
      immunofluorescence. RESULTS: TNF-alpha and NF-kappaB-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-kappaB-P65, p-IKK and p-IkappaBalpha 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-kappaB-P65, p-IKK and p-IkappaBalpha but increased the 
      expression of E-cadherin. Moreover, metformin inhibited NF-kappaB-P65 translocation 
      into the nucleus. CONCLUSIONS: TNF-alpha accelerated the EMT process potentially via 
      activation of the NF-kappaB signaling pathway. Metformin might suppress TNF-alpha-induced 
      EMT in prostate cancer by inactivating the NF-kappaB signaling pathway.
CI  - 2020 Translational Cancer Research. All rights reserved.
FAU - Wang, Min
AU  - Wang M
AD  - Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, 
      Wuhan, China.
FAU - Liu, Xiuheng
AU  - Liu X
AD  - Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, 
      Wuhan, China.
FAU - Chen, Zhiyuan
AU  - Chen Z
AD  - Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, 
      Wuhan, China.
FAU - Chen, Hui
AU  - Chen H
AD  - Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, 
      Wuhan, China.
FAU - Tan, Yifan
AU  - Tan Y
AD  - Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, 
      Wuhan, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Transl Cancer Res
JT  - Translational cancer research
JID - 101585958
PMC - PMC8798386
OTO - NOTNLM
OT  - Metformin
OT  - NF-kappaB
OT  - Tumor necrosis factor-alpha (TNF-alpha)
OT  - epithelial-mesenchymal transition (EMT)
OT  - prostate cancer (PCa)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at http://dx.doi.org/10.21037/tcr-20-1186). The authors have no 
      conflicts of interest to declare.
EDAT- 2020/10/01 00:00
MHDA- 2020/10/01 00:01
PMCR- 2020/10/01
CRDT- 2022/02/04 05:50
PHST- 2020/02/24 00:00 [received]
PHST- 2020/08/10 00:00 [accepted]
PHST- 2022/02/04 05:50 [entrez]
PHST- 2020/10/01 00:00 [pubmed]
PHST- 2020/10/01 00:01 [medline]
PHST- 2020/10/01 00:00 [pmc-release]
AID - tcr-09-10-6086 [pii]
AID - 10.21037/tcr-20-1186 [doi]
PST - ppublish
SO  - Transl Cancer Res. 2020 Oct;9(10):6086-6095. doi: 10.21037/tcr-20-1186.