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

2020 ◽  
Vol 13 (10) ◽  
pp. 315
Author(s):  
Maritza P. Garrido ◽  
Renato Salvatierra ◽  
Manuel Valenzuela-Valderrama ◽  
Christopher Vallejos ◽  
Nicole Bruneau ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Epithelial Ovarian Cancer ◽  
Complementary Therapy ◽  
Ovarian Cancer Cells ◽  
Angiogenic Potential ◽  
Skov3 Cells ◽  
High Affinity Receptor ◽  
Ovarian Surface Epithelial

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.

scholarly journals Metformin prevents nerve growth factor-dependent proliferative and proangiogenic effects in epithelial ovarian cancer cells and endothelial cells

2018 ◽  
Vol 10 ◽  
pp. 175883591877098 ◽  
Author(s):  
Maritza P. Garrido ◽  
Carolina Vera ◽  
Margarita Vega ◽  
Andrew F.G. Quest ◽  
Carmen Romero
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Epithelial Ovarian Cancer ◽  
Ovarian Cancer Cells ◽  
Nerve Growth ◽  
Angiogenic Potential ◽  
Ea.Hy926 Cells

Background: Epithelial ovarian cancer (EOC) is characterized by exacerbated angiogenesis regulated by proangiogenic and growth factors. Nerve growth factor (NGF) is overexpressed in EOC where it promotes proliferation as well as survival and is considered a proangiogenic factor. Metformin, a drug commonly used in the treatment of diabetes, is attributed to antineoplastic effects, but the underlying mechanisms remain unknown. Given that current therapies yield modest results in EOC patients, the aim of this study was to determine the effects of metformin on NGF-enhanced proliferation of EOC cells and the angiogenic potential of endothelial cells. Methods: A2780 (EOC), HOSE (human ovarian surface epithelial) and EA.hy926 (endothelial) cells were treated with NGF and metformin. Cell viability, cell proliferation and cell cycle were evaluated in all three cell lines, and the angiogenic potential in endothelial EA.hy926 cells. Results: NGF enhanced cell proliferation in A2780, HOSE and EA.hy926 cells ( p < 0.05), while metformin treatment decreased cell proliferation in A2780 and EA.hy926 cells ( p < 0.05). Moreover, the NGF-enhanced angiogenic score in EA.hy926 cells was prevented by metformin ( p < 0.05). Conclusions: Given that NGF plays a significant role in EOC progression, our current findings suggest that metformin holds considerable promise as an adjuvant treatment in ovarian cancer.

scholarly journals MiR-200c-3p Contrasts PD-L1 Induction by Combinatorial Therapies and Slows Proliferation of Epithelial Ovarian Cancer through Downregulation of β-Catenin and c-Myc

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 519
Author(s):  
Eleni Anastasiadou ◽  
Elena Messina ◽  
Tiziana Sanavia ◽  
Lucia Mundo ◽  
Federica Farinella ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Therapeutic Strategy ◽  
Target Genes ◽  
Ovarian Cancer Cells ◽  
Oncogenic Signaling ◽  
Experimental Conditions ◽  
Skov3 Cells ◽  
In Silico Analyses ◽  
Post Therapy

Conventional/targeted chemotherapies and ionizing radiation (IR) are being used both as monotherapies and in combination for the treatment of epithelial ovarian cancer (EOC). Several studies show that these therapies might favor oncogenic signaling and impede anti-tumor responses. MiR-200c is considered a master regulator of EOC-related oncogenes. In this study, we sought to investigate if chemotherapy and IR could influence the expression of miR-200c-3p and its target genes, like the immune checkpoint PD-L1 and other oncogenes in a cohort of EOC patients’ biopsies. Indeed, PD-L1 expression was induced, while miR-200c-3p was significantly reduced in these biopsies post-therapy. The effect of miR-200c-3p target genes was assessed in miR-200c transfected SKOV3 cells untreated and treated with olaparib and IR alone. Under all experimental conditions, miR-200c-3p concomitantly reduced PD-L1, c-Myc and β-catenin expression and sensitized ovarian cancer cells to olaparib and irradiation. In silico analyses further confirmed the anti-correlation between miR-200c-3p with c-Myc and β-catenin in 46 OC cell lines and showed that a higher miR-200c-3p expression associates with a less tumorigenic microenvironment. These findings provide new insights into how miR-200c-3p could be used to hold in check the adverse effects of conventional chemotherapy, targeted therapy and radiation therapy, and offer a novel therapeutic strategy for EOC.

Antagonists of Growth Hormone-Releasing Hormone and Somatostatin Analog RC-160 Inhibit the Growth of the OV-1063 Human Epithelial Ovarian Cancer Cell Line Xenografted into Nude Mice1

2001 ◽  
Vol 86 (5) ◽  
pp. 2144-2152
Author(s):  
Ioulia Chatzistamou ◽  
Andrew V. Schally ◽  
Jozsef L. Varga ◽  
Kate Groot ◽  
Patricia Armatis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Serum Insulin ◽  
Ovarian Cancer Cell Line ◽  
Somatostatin Analog ◽  
Ovarian Cancer Cells ◽  
Messenger Ribonucleic Acid ◽  
Igf I ◽  
Ghrh Antagonists

The effects of antagonists of GHRH and the somatostatin analog RC-160 on the growth of OV-1063 human epithelial ovarian cancer cells xenografted into nude mice were investigated. Treatment with 20μ g/day of the GHRH antagonist JV-1-36 or MZ-5-156 and 60 μg/day of the somatostatin analog RC-160 for 25 days decreased tumor volume by 70.9% (P &lt; 0.01), 58.3% (P&lt; 0.05), and 60.6% (P &lt; 0.01), respectively, vs. the control value. The levels of GH in serum were decreased in all of the treated groups, but only RC-160 significantly reduced serum insulin-like growth factor I (IGF-I). The levels of messenger ribonucleic acid (mRNA) for IGF-I and -II and for their receptors in OV-1063 tumors were investigated by multiplex RT-PCR. No expression of mRNA for IGF-I was detected, but treatment with JV-1-136 caused a 51.8% decrease (P &lt; 0.05) in the level of mRNA for IGF-II in tumors. Exposure of OV-1063 cells cultured in vitro to GHRH, IGF-I, or IGF-II significantly (P &lt; 0.05) stimulated cell growth, but 10−5 mol/L JV-1-36 nearly completely inhibited (P &lt; 0.001) OV-1063 cell proliferation. OV-1063 tumors expressed mRNA for GHRH receptors and showed the presence of binding sites for GHRH. Our results indicate that antagonistic analogs of GHRH and the somatostatin analog RC-160 inhibit the growth of epithelial ovarian cancers. The effects of RC-160 seem to be exerted more on the pituitary GH-hepatic IGF-I axis, whereas GHRH antagonists appear to reduce IGF-II production and interfere with the autocrine regulatory pathway. The antitumorigenic action of GHRH antagonists appears to be mediated by GHRH receptors found in OV-1063 tumors.

scholarly journals Identification of Novel Drug Candidate for Epithelial Ovarian Cancer via In Silico Investigation and In Vitro Validation

2021 ◽  
Vol 11 ◽  
Author(s):  
Dan Zou ◽  
Jin Bai ◽  
Enting Lu ◽  
Chunjiao Yang ◽  
Jiaqing Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Molecular Docking ◽  
Epithelial Ovarian Cancer ◽  
Drug Candidate ◽  
Hub Genes ◽  
Western Blots ◽  
Skov3 Cells ◽  
Novel Drug

Epithelial ovarian cancer (EOC) has a poor prognosis and high mortality rate; patients are easy to relapse with standard therapies. So, there is an urgent need to develop novel drugs. In this study, differentially expressed genes (DEGs) of EOC were identified in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Enrichment and protein–protein interaction (PPI) analyses were performed. The drug candidate which has the possibility to treat EOC was predicted by Connectivity Map (CMAP) databases. Moreover, molecular docking was selected to calculate the binding affinity between drug candidate and hub genes. The cytotoxicity of drug candidates was assessed by MTT and colony formation analysis, the proteins coded by hub genes were detected by Western blots, and apoptosis analysis was evaluated by flow cytometry. Finally, 296 overlapping DEGs (|log 2 fold change|&gt;1; q-value &lt;0.05), which were principally involved in the cell cycle (p &lt; 0.05), and cyclin-dependent kinase 1 (CDK1) were screened as the significant hub gene from the PPI network. Furthermore, the 21 drugs were extracted from CMAPs; among them, piperlongumine (PL) showed a lower CMAP score (-0.80, -62.92) and was regarded as the drug candidate. Furthermore, molecular docking results between PL and CDK1 with a docking score of –8.121 kcal/mol were close to the known CDK1 inhibitor (–8.24 kcal/mol). Additionally, in vitro experiments showed that PL inhibited proliferation and induced apoptosis via targeting CDK1 in EOC SKOV3 cells. Our results reveal that PL may be a novel drug candidate for EOC by inhibiting cell cycle.

scholarly journals Role of Mitochondria in Interplay between NGF/TRKA, miR-145 and Possible Therapeutic Strategies for Epithelial Ovarian Cancer

Life ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 8
Author(s):  
Daniela B. Vera ◽  
Allison N. Fredes ◽  
Maritza P. Garrido ◽  
Carmen Romero
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Epithelial Ovarian Cancer ◽  
Therapeutic Strategies ◽  
Apoptotic Pathway ◽  
Invasion And Migration ◽  
High Affinity Receptor ◽  
And Migration ◽  
Laboratory Group

Ovarian cancer is the most lethal gynecological neoplasm, and epithelial ovarian cancer (EOC) accounts for 90% of ovarian malignancies. The 5-year survival is less than 45%, and, unlike other types of cancer, the proportion of women who die from this disease has not improved in recent decades. Nerve growth factor (NGF) and tropomyosin kinase A (TRKA), its high-affinity receptor, play a crucial role in pathogenesis through cell proliferation, angiogenesis, invasion, and migration. NGF/TRKA increase their expression during the progression of EOC by upregulation of oncogenic proteins as vascular endothelial growth factor (VEGF) and c-Myc. Otherwise, the expression of most oncoproteins is regulated by microRNAs (miRs). Our laboratory group reported that the tumoral effect of NGF/TRKA depends on the regulation of miR-145 levels in EOC. Currently, mitochondria have been proposed as new therapeutic targets to activate the apoptotic pathway in the cancer cell. The mitochondria are involved in a myriad of functions as energy production, redox control, homeostasis of Ca+2, and cell death. We demonstrated that NGF stimulation produces an augment in the Bcl-2/BAX ratio, which supports the anti-apoptotic effects of NGF in EOC cells. The review aimed to discuss the role of mitochondria in the interplay between NGF/TRKA and miR-145 and possible therapeutic strategies that may decrease mortality due to EOC.

Knockdown of Rab25 expression by RNAi inhibits growth of human epithelial ovarian cancer cells in vitro and in vivo

Pathology ◽  
2006 ◽  
Vol 38 (6) ◽  
pp. 561-567 ◽  
Author(s):  
Fan Yang ◽  
Xin Xiao-Yan ◽  
Chen Bi-Liang ◽  
Ma Xiangdong
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells

Picropodophyllin inhibits epithelial ovarian cancer cells in vitro and in vivo

2013 ◽  
Vol 435 (3) ◽  
pp. 385-390 ◽  
Author(s):  
Xiaosheng Lu ◽  
Ledan Wang ◽  
Jie Mei ◽  
Xin Wang ◽  
Xueqiong Zhu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells
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