{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:13:25Z","timestamp":1789647205077,"version":"4.0.0"},"reference-count":61,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico - FONDECYT","award":["1130250"],"award-info":[{"award-number":["1130250"]}]},{"name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico - FONDECYT","award":["1160139"],"award-info":[{"award-number":["1160139"]}]},{"name":"Comisi\u00f3n Nacional de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica - FONDAP","award":["15130011"],"award-info":[{"award-number":["15130011"]}]},{"name":"Comisi\u00f3n Nacional de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica - Scolarship","award":["21150360"],"award-info":[{"award-number":["21150360"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>NGF enhanced cell proliferation in A2780, HOSE and EA.hy926 cells ( p &lt; 0.05), while metformin treatment decreased cell proliferation in A2780 and EA.hy926 cells ( p &lt; 0.05). Moreover, the NGF-enhanced angiogenic score in EA.hy926 cells was prevented by metformin ( p &lt; 0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1758835918770984","type":"journal-article","created":{"date-parts":[[2018,5,4]],"date-time":"2018-05-04T08:23:06Z","timestamp":1525422186000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":26,"title":["Metformin prevents nerve growth factor-dependent proliferative and proangiogenic effects in epithelial ovarian cancer cells and endothelial cells"],"prefix":"10.1177","volume":"10","author":[{"given":"Maritza P.","family":"Garrido","sequence":"first","affiliation":[{"name":"Laboratory of Endocrinology and Reproductive Biology, Hospital Cl\u00ednico Universidad de Chile, Santiago, Chile Obstetrics and Gynecology Department, Medicine School, Universidad de Chile, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Vera","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Reproductive Biology, Hospital Cl\u00ednico Universidad de Chile, Santiago, Chile Obstetrics and Gynecology Department, Medicine School, Universidad de Chile, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Vega","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Reproductive Biology, Hospital Cl\u00ednico Universidad de Chile, Santiago, Chile Obstetrics and Gynecology Department, Medicine School, Universidad de Chile, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F.G.","family":"Quest","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad de Chile, Santiago, Chile Laboratorio de Comunicaciones Celulares, Centro de Centro de estudios en Ejercicio, Metabolismo y C\u00e1ncer (CEMC) Programa de Biolog\u00eda Celular y Molecular, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad De Medicina, Universidad de Chile, Santiago, Chile Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Romero","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico Universidad de Chile, Santos Dumont 999, Santiago 8380456, Chile; Laboratory of Endocrinology and Reproductive Biology, Hospital Cl\u00ednico Universidad de Chile, Santiago, Chile; Obstetrics and Gynecology Department, Medicine School, Universidad de Chile, Santiago, Chile; Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,5,4]]},"reference":[{"key":"bibr1-1758835918770984","doi-asserted-by":"publisher","DOI":"10.3945\/an.116.012211"},{"key":"bibr2-1758835918770984","first-page":"255","volume":"22","author":"Auersperg N","year":"2001","journal-title":"Endocr Rev"},{"key":"bibr3-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1136\/mp.55.6.348"},{"key":"bibr4-1758835918770984","unstructured":"Cancer Research UK. Ovarian cancer: survival, http:\/\/www.cancerresearchuk.org\/about-cancer\/ovarian-cancer\/survival (2006, accessed 12 April 2018)."},{"key":"bibr5-1758835918770984","unstructured":"The American Cancer Society. Survival rates for ovarian cancer, by stage, https:\/\/www.cancer.org\/cancer\/ovarian-cancer\/detection-diagnosis-staging\/survival-rates.html (2017, accessed 4 February 2016)."},{"key":"bibr6-1758835918770984","doi-asserted-by":"publisher","DOI":"10.3802\/jgo.2017.28.e45"},{"key":"bibr7-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-31-14"},{"key":"bibr8-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gav057"},{"key":"bibr9-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1017\/S0967199412000111"},{"key":"bibr10-1758835918770984","unstructured":"Leung P. The ovary. 2nd ed. San Diego, CA: Academic Press, 2004, p.3\u201323."},{"key":"bibr11-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2006.07.007"},{"key":"bibr12-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2010.12.341"},{"key":"bibr13-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1304617"},{"key":"bibr14-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-014-0082-6"},{"key":"bibr15-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1126\/science.3306916"},{"key":"bibr16-1758835918770984","doi-asserted-by":"publisher","DOI":"10.2174\/156720207780637216"},{"key":"bibr17-1758835918770984","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.4075"},{"key":"bibr18-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2008.09.010"},{"key":"bibr19-1758835918770984","doi-asserted-by":"publisher","DOI":"10.3132\/dvdr.2008.027"},{"key":"bibr20-1758835918770984","doi-asserted-by":"publisher","DOI":"10.7573\/dic.212282"},{"key":"bibr21-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38415.708634.F7"},{"key":"bibr22-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2011.06.038"},{"key":"bibr23-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27706"},{"key":"bibr24-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3182393ab3"},{"key":"bibr25-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-9-33"},{"key":"bibr26-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-015-0273-5"},{"key":"bibr27-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-015-0598-8"},{"key":"bibr28-1758835918770984","first-page":"57","volume":"2","author":"Kasznicki J","year":"2014","journal-title":"Ann Transl Med"},{"key":"bibr29-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210421"},{"key":"bibr30-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209100"},{"key":"bibr31-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2006.1894"},{"key":"bibr32-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-15-0068"},{"key":"bibr33-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-28-16"},{"key":"bibr34-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-016-0395-y"},{"key":"bibr35-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-4-57"},{"key":"bibr36-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2010.12.002"},{"key":"bibr37-1758835918770984","unstructured":"U.S. National Institutes of Health. An observational study of avastin (bevacizumab) in combination with carboplatin\/paclitaxel in first line in patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer (OTILIA), https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01697488?term=bevacizumab&recrs=a&cond=ovarian+cancer&draw=2&rank=27 (2017, accessed 1 February 2018)."},{"key":"bibr38-1758835918770984","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13310"},{"key":"bibr39-1758835918770984","first-page":"85","volume":"25","author":"Witsch E","year":"2010","journal-title":"Physiology (Bethesda)"},{"key":"bibr40-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-015-0249-0"},{"key":"bibr41-1758835918770984","first-page":"484","volume":"21","author":"Huo J","year":"2017","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"bibr42-1758835918770984","doi-asserted-by":"publisher","DOI":"10.3892\/or.2012.1890"},{"key":"bibr43-1758835918770984","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2015.3004"},{"key":"bibr44-1758835918770984","unstructured":"United States Food and Drug Administration. Glumetza\u2122, 500 mg (metformin hydrochloride extended release tablets), https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2006\/021748s002lbl.pdf3-18 (2006, accessed 12 April 2018)."},{"key":"bibr45-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12525"},{"key":"bibr46-1758835918770984","doi-asserted-by":"publisher","DOI":"10.3109\/00498259409043220"},{"key":"bibr47-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.034140"},{"key":"bibr48-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0145"},{"key":"bibr49-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1038\/srep20508"},{"key":"bibr50-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13505"},{"key":"bibr51-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.12.001"},{"key":"bibr52-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.742247"},{"key":"bibr53-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-013-1144-8"},{"key":"bibr54-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2009.00954.x"},{"key":"bibr55-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002309"},{"key":"bibr56-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-009-9780-3"},{"key":"bibr57-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.662114"},{"key":"bibr58-1758835918770984","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8595"},{"key":"bibr59-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12435"},{"key":"bibr60-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.1.223"},{"key":"bibr61-1758835918770984","doi-asserted-by":"publisher","DOI":"10.1042\/bj3480607"}],"container-title":["Therapeutic Advances in Medical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1758835918770984","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1758835918770984","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1758835918770984","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:22:20Z","timestamp":1777587740000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1758835918770984"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,1]]},"references-count":61,"alternative-id":["10.1177\/1758835918770984"],"URL":"https:\/\/doi.org\/10.1177\/1758835918770984","relation":{},"ISSN":["1758-8359","1758-8359"],"issn-type":[{"value":"1758-8359","type":"print"},{"value":"1758-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,1]]},"article-number":"1758835918770984"}}