Antitumoral Effect of Plocabulin in High Grade Serous Ovarian Carcinoma Cell Line Models

Frontiers in Oncology

Jaime Feliu¹  Andrés Redondo¹  Marta Martínez-Díez²  Victoria Heredia-Soto³  Alejandro Gallego⁴  David Hardisson⁷  Alicia Hernández⁷  Alberto Berjón⁸  Marta Mendiola⁸  Shuyu Zheng⁹  Jing Tang⁹  María Miguel^1,10  Javier Escudero^1,10  Patricia Ruiz^1,10 

[1] 0Cátedra UAM-ANGEM, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain;Cell Biology Department, Research and Development, Oncology Business Unit, Pharmamar, Madrid, Spain;Center for Biomedical Research in the Cancer Network (Centro de Investigación Biomédica en Red de Cáncer, CIBERONC), Instituto de Salud Carlos III, Madrid, Spain;Department of Medical Oncology, Hospital Universitario La Paz, Madrid, Spain;Department of Obstetrics and Gynecology, Hospital Universitario La Paz, Madrid, Spain;Department of Pathology, Hospital Universitario La Paz, Madrid, Spain;Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain;Molecular Pathology and Therapeutic Targets Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain;Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland;Translational Oncology Research Laboratory, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain;

关键词: plocabulin (PM060184);    microtubule inhibitor;    high-grade serous ovarian cancer (HGSOC);    3D cell culture;    drug testing;   

DOI  :  10.3389/fonc.2022.862321

来源: DOAJ

【 摘 要 】

Ovarian cancer (OC) is a life-threatening tumor and the deadliest among gynecological cancers in developed countries. First line treatment with a carboplatin/paclitaxel regime is initially effective in the majority of patients, but most advanced OC will recur and develop drug resistance. Therefore, the identification of alternative therapies is needed. In this study, we employed a panel of high-grade serous ovarian cancer (HGSOC) cell lines, in monolayer and three-dimensional cell cultures. We evaluated the effects of a novel tubulin-binding agent, plocabulin, on proliferation, cell cycle, migration and invasion. We have also tested combinations of plocabulin with several drugs currently used in OC in clinical practice. Our results show a potent antitumor activity of plocabulin, inhibiting proliferation, disrupting microtubule network, and decreasing their migration and invasion capabilities. We did not observe any synergistic combination of plocabulin with cisplatin, doxorubicin, gemcitabine or trabectedin. In conclusion, plocabulin has a potent antitumoral effect in HGSOC cell lines that warrants further clinical investigation.

【 授权许可】

Unknown