Synergistic Effects of Morin and Doxorubicin Overcome Chemoresistance in Ovarian Cancer: Preclinical Insights From in vitro and in vivo Models
Year: 2026
Type: article
Abstract: Ruihua Wu,1 Amirabas Bostani,2 Junmei Wang3 1Department of Obstetrics and Gynecology, Xi’an People’s Hospital (Xi’an Fourth Hospital), Xi’an, 710000, People’s Republic of China; 2Department of Biology, Science & Research Institute, Islamic Azad University, Tehran, Iran; 3Department of Obstetrics and Gynecology, XD Group Hospital, Xi’an, 710000, People’s Republic of ChinaCorrespondence: Junmei Wang, Department of Obstetrics and Gynecology, XD Group Hospital, Xi’an, 710000, People’s Republic of China, Tel +86 3319206720, Email [email protected]: Epithelial ovarian cancer (EOC) remains highly lethal due to late-stage diagnosis and chemoresistance, necessitating strategies to enhance conventional therapies like doxorubicin (DOX) while mitigating toxicity. This study evaluated morin, a flavonoid, as an adjunct to DOX in chemoresistant EOC models.Methods: In vitro, DOX-resistant OVCAR-3-DR, OVCAR-3, and A2780 cells were treated with DOX, morin, or their combination. Synergy was assessed via MTT and apoptosis assays, alongside autophagy and cell cycle markers. In vivo, OVCAR-3-DR xenograft mice were divided into Sham, DOX (5 mg/kg), morin (15 and 30 mg/Kg), and combination groups. Tumor volume, apoptosis (BCL-2, caspase-3/9), autophagy (LC3, ATG5, Beclin-1), cell cycle regulators (Cyclin A2/D1), and oxidative stress (SOD, CAT, GPx, GR, GSH, MDA) were analyzed.Results: Findings demonstrated significant synergistic cytotoxicity, with a combination index (CI) of 0.72, and enhanced apoptosis. Combination therapy suppressed Cyclin A2/D1, upregulated autophagy markers (, and reduced oxidative stress. In vivo, DOX+Morin30 reduced tumor volume synergistically (p< 0.001) without systemic toxicity (stable body weight).Conclusion: Morin synergizes with DOX by modulating apoptosis, autophagy, cell cycle, and oxidative stress, overcoming chemoresistance while reducing toxicity. These findings position morin as a promising, orally bioavailable adjunct worthy of further clinical investigation for optimizing DOX therapy in refractory EOC.Keywords: ovarian neoplasms, flavonoids, drug resistance, apoptosis, autophagy, xenograft model antitumor assays
Authors: Wu R, Bostani A, Wang J
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7120793370
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