Metformin Reduces NGF-Induced Tumour Promoter Effects in Epithelial Ovarian Cancer Cells

Epithelial ovarian cancer (EOC) is a lethal gynaecological neoplasm characterized by rapid growth and angiogenesis. Nerve growth factor (NGF) and its high affinity receptor tropomyosin receptor kinase A (TRKA) contribute to EOC progression by increasing the expression of c-MYC, survivin and vascular...

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Hoofdauteurs: Maritza P. Garrido (Auteur), Renato Salvatierra (Auteur), Manuel Valenzuela-Valderrama (Auteur), Christopher Vallejos (Auteur), Nicole Bruneau (Auteur), Andrea Hernández (Auteur), Margarita Vega (Auteur), Alberto Selman (Auteur), Andrew F. G. Quest (Auteur), Carmen Romero (Auteur)
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Gepubliceerd in: MDPI AG, 2020-10-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Maritza P. Garrido  |e author 
700 1 0 |a Renato Salvatierra  |e author 
700 1 0 |a Manuel Valenzuela-Valderrama  |e author 
700 1 0 |a Christopher Vallejos  |e author 
700 1 0 |a Nicole Bruneau  |e author 
700 1 0 |a Andrea Hernández  |e author 
700 1 0 |a Margarita Vega  |e author 
700 1 0 |a Alberto Selman  |e author 
700 1 0 |a Andrew F. G. Quest  |e author 
700 1 0 |a Carmen Romero  |e author 
245 0 0 |a Metformin Reduces NGF-Induced Tumour Promoter Effects in Epithelial Ovarian Cancer Cells 
260 |b MDPI AG,   |c 2020-10-01T00:00:00Z. 
500 |a 10.3390/ph13100315 
500 |a 1424-8247 
520 |a Epithelial ovarian cancer (EOC) is a lethal gynaecological neoplasm characterized by rapid growth and angiogenesis. Nerve growth factor (NGF) and its high affinity receptor tropomyosin receptor kinase A (TRKA) contribute to EOC progression by increasing the expression of c-MYC, survivin and vascular endothelial growth factor (VEGF) along with a decrease in microRNAs (miR) 23b and 145. We previously reported that metformin prevents NGF-induced proliferation and angiogenic potential of EOC cells. In this study, we sought to obtain a better understanding of the mechanism(s) by which metformin blocks these NGF-induced effects in EOC cells. Human ovarian surface epithelial (HOSE) and EOC (A2780/SKOV3) cells were stimulated with NGF and/or metformin to assess the expression of c-MYC, β-catenin, survivin and VEGF and the abundance of the tumor suppressor miRs 23b and 145. Metformin decreased the NGF-induced transcriptional activity of MYC and β-catenin/T-cell factor/lymphoid enhancer-binding factor (TCF-Lef), as well as the expression of c-MYC, survivin and VEGF in EOC cells, while it increased miR-23b and miR-145 levels. The preliminary analysis of ovarian biopsies from women users or non-users of metformin was consistent with these in vitro results. Our observations shed light on the mechanisms by which metformin may suppress tumour growth in EOC and suggest that metformin should be considered as a possible complementary therapy in EOC treatment. 
546 |a EN 
690 |a metformin 
690 |a epithelial ovarian cancer 
690 |a NGF 
690 |a VEGF 
690 |a survivin 
690 |a c-MYC 
690 |a Medicine 
690 |a R 
690 |a Pharmacy and materia medica 
690 |a RS1-441 
655 7 |a article  |2 local 
786 0 |n Pharmaceuticals, Vol 13, Iss 10, p 315 (2020) 
787 0 |n https://www.mdpi.com/1424-8247/13/10/315 
787 0 |n https://doaj.org/toc/1424-8247 
856 4 1 |u https://doaj.org/article/b346f67ac0a948d7b82a12b3b9f8dfa4  |z Connect to this object online.