@article{fed75a6e642b4fd49cc296e08f1f74a4,
title = "Biguanides in combination with olaparib limits tumorigenesis of drug-resistant ovarian cancer cells through inhibition of Snail",
abstract = "Ovarian cancer is the most lethal gynecological malignancy. Currently, new chemotherapeutic strategies are required to improve patient outcome and survival. Biguanides, classic anti-diabetic drugs, have gained importance for theiri antitumor potency demonstrated by various studies. Olaparib is a PARP inhibitor approved for maintenance therapy following platinum-based chemotherapy. Furthermore, Snai1, a transcription factor that works as a master regulator of the epithelial/mesenchymal transition process (EMT) is involved in ovarian cancer resistance and progression. Here we aimed to demonstrate the possible cross talk between biguanides and Snail in response to olaparib combination therapy. In this study, we have shown that while in A2780CR cells biguanides reduced cell survival (single treatments ~20%; combined treatment ~44%) and cell migration (single treatments ~45%; biguanide-olaparib ~80%) significantly, A2780PAR exhibited superior efficacy with single (~60%) and combined treatments (~80%). Moreover, our results indicate that knock-down of Snail further enhances the attenuation of migration, inhibits EMT related-proteins (~90%) and induces a synergistic effect in biguanide-olaparib treatment. Altogether, this work suggests a novel treatment strategy against drug-resistant or recurrent ovarian cancer.",
keywords = "EMT, PARP inhibitors, combined therapy, metastatic ovarian cancer, transcription factor",
author = "Qiong Wang and L{\'o}pez-Ozuna, {Vanessa M.} and Tahira Baloch and Joanne Bithras and Oreekha Amin and Roy Kessous and Liron Kogan and Ido Laskov and Amber Yasmeen",
note = "Funding Information: Part of this study was supported by the International Training Program of Guangzhou (China) Postdoctoral Research Fellow (Qiong Wang) in 2017 (ITPGPRF‐2017). Moreover, the authors thank Dr Kun Shi from the Department of Gynecology and Obstetrics and Dr Gendie E. Lash from the Division of Uterine Vascular Biology, Guangzhou Institute of Pediatrics, the Guangzhou Women and Children's Medical Center, Guangzhou, China, for their kind assistance in ITPGPRF‐2017 application. Joanna Bithras was supported by FRN53888‐CIHR/FRSQ grant obtained from McGill Integrated Cancer Research Training Program. This work was made possible in part by grants from the Montreal‐Israel Cancer Research Foundation, the Gloria's Girls and the Susan and Jonathan Fund. The funding bodies had no role in the design of the study, collection, analysis, and interpretation of data and in writing of the manuscript. Funding Information: Part of this study was supported by the International Training Program of Guangzhou (China) Postdoctoral Research Fellow (Qiong Wang) in 2017 (ITPGPRF-2017). Moreover, the authors thank Dr Kun Shi from the Department of Gynecology and Obstetrics and Dr Gendie E. Lash from the Division of Uterine Vascular Biology, Guangzhou Institute of Pediatrics, the Guangzhou Women and Children's Medical Center, Guangzhou, China, for their kind assistance in ITPGPRF-2017 application. Joanna Bithras was supported by FRN53888-CIHR/FRSQ grant obtained from McGill Integrated Cancer Research Training Program. This work was made possible in part by grants from the Montreal-Israel Cancer Research Foundation, the Gloria's Girls and the Susan and Jonathan Fund. The funding bodies had no role in the design of the study, collection, analysis, and interpretation of data and in writing of the manuscript. Publisher Copyright: {\textcopyright} 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.",
year = "2020",
month = feb,
day = "1",
doi = "10.1002/cam4.2738",
language = "English",
volume = "9",
pages = "1307--1320",
journal = "Cancer Medicine",
issn = "2045-7634",
publisher = "John Wiley and Sons Ltd",
number = "4",
}
