What question did this study set out to answer?

The research aims to investigate how morin can enhance the effectiveness of doxorubicin in overcoming chemoresistance in ovarian cancer.

January 10, 2026Cancer Management and Research0 citationsOpen Access

Synergistic Effects of Morin and Doxorubicin Overcome Chemoresistance in Ovarian Cancer: Preclinical Insights From in vitro and in vivo Models

RWRuihua WuThe Fourth People's Hospital ABAmirabas Bostani JWJunmei WangChina XD Group (China)

Key Result

The combination of morin and doxorubicin significantly reduced tumor volume by p<0.001 in chemoresistant ovarian cancer without systemic toxicity.

Key Points

The research aims to investigate how morin can enhance the effectiveness of doxorubicin in overcoming chemoresistance in ovarian cancer.
Conducted in vitro experiments with ovarian cancer cell lines
Utilized in vivo models to assess treatment efficacy
Analyzed the interaction between morin and doxorubicin
Morin significantly increased sensitivity to doxorubicin in ovarian cancer cells
Combination treatment reduced tumor growth in animal models
Mechanistic studies indicated altered apoptotic pathways

Structured PICO

Does the combination of morin and doxorubicin improve cytotoxicity and reduce tumor volume in chemoresistant ovarian cancer models compared to monotherapy?

Population

In vitro human ovarian cancer cell lines (A2780, OVCAR-3, and DOX-resistant OVCAR-3-DR) and in vivo female athymic BALB/c nude mice (6-8 weeks old, 18-22 g) bearing OVCAR-3-DR xenografts (n=48).

Intervention

Doxorubicin (5 mg/kg intraperitoneally every 3 days) combined with morin (15 or 30 mg/kg orally once daily) for 22 days in vivo; doxorubicin (1 µM) combined with morin (50 µM) in vitro.

Comparator

Sham (intraperitoneal 0.9% NaCl and oral 0.5% carboxymethyl cellulose), doxorubicin monotherapy (5 mg/kg), and morin monotherapy (15 or 30 mg/kg).

Outcome

Tumor volume (in vivo) and cell viability/cytotoxicity (in vitro).surrogate

Morin is a promising, orally bioavailable adjunct that synergistically enhances doxorubicin efficacy and overcomes chemoresistance in ovarian cancer models without adding systemic toxicity.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Background: 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.

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