Next Article in Journal
Novel Photosensitizer β-Mannose-Conjugated Chlorin e6 as a Potent Anticancer Agent for Human Glioblastoma U251 Cells
Previous Article in Journal
Medicinal Plants to Strengthen Immunity during a Pandemic
Previous Article in Special Issue
Metformin: A Potential Therapeutic Tool for Rheumatologists
Open AccessCommunication

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

1
Laboratorio de Endocrinología y Biología de la Reproducción, Hospital Clínico Universidad de Chile, Santiago 8380456, Chile
2
Departamento de Obstetricia y Ginecología, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
3
Laboratorio de Microbiología Celular, Instituto de Investigación e Innovación en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago 8320000, Chile
4
Instituto Nacional del Cáncer, Santiago 8380455, Chile
5
Laboratorio de Comunicaciones Celulares, Centro de estudios en Ejercicio, Metabolismo y Cáncer (CEMC), Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas (ICBM), Facultad De Medicina, Universidad de Chile, Santiago 8380453, Chile
6
Advanced Center for Chronic Diseases (ACCDiS), Santiago 8380000, Chile
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(10), 315; https://doi.org/10.3390/ph13100315
Received: 30 June 2020 / Revised: 22 September 2020 / Accepted: 24 September 2020 / Published: 16 October 2020
(This article belongs to the Special Issue Metformin: Mechanism and Application 2020)
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. View Full-Text
Keywords: metformin; epithelial ovarian cancer; NGF; VEGF; survivin; c-MYC; β-catenin metformin; epithelial ovarian cancer; NGF; VEGF; survivin; c-MYC; β-catenin
Show Figures

Figure 1

MDPI and ACS Style

Garrido, M.P.; Salvatierra, R.; Valenzuela-Valderrama, M.; Vallejos, C.; Bruneau, N.; Hernández, A.; Vega, M.; Selman, A.; Quest, A.F.G.; Romero, C. Metformin Reduces NGF-Induced Tumour Promoter Effects in Epithelial Ovarian Cancer Cells. Pharmaceuticals 2020, 13, 315.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop