A Novel Approach to Overcome Cisplatin Resistance in Ovarian Cancer: Revealing the Synergistic Potential of Quercetin-Loaded Solid Lipid Nanoparticles

Shamsi, Masoumeh; Babaahmadi-Rezaei, Hossien; Khedri, Azam; Hatami, Mahdi; Rashidi, Mojtaba

doi:10.61882/ibj.4543

A Novel Approach to Overcome Cisplatin Resistance in Ovarian Cancer: Revealing the Synergistic Potential of Quercetin-Loaded Solid Lipid Nanoparticles

Authors

Masoumeh Shamsi ¹

Hossien Babaahmadi-Rezaei ²

Azam Khedri ¹

Mahdi Hatami ²

Mojtaba Rashidi ¹

¹ Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

² Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

10.61882/ibj.4543

Abstract

Background: Ovarian cancer (OC) remains the leading cause of mortality among gynecological cancers, mainly because of resistance to platinum-based chemotherapy, particularly cisplatin. This study investigated the potential of quercetin (QU)-loaded solid lipid nanoparticles (SLNs) to address cisplatin resistance in OC cells.

Methods: The efficacy of QU-SLN was assessed in vitro on the cisplatin-resistant SK-OV-3 and cisplatin-sensitive A2780s human OC cell lines. Various assays, including cytotoxicity, cell viability, clonogenicity, flow cytometry, quantitative RT-PCR, and wound healing assays, evaluated the combined effects of QU and QU-SLN with cisplatin on cell viability, apoptosis, gene expression levels related to cisplatin resistance, and cell migration.

Results: Combining QU-SLN with cisplatin resulted in significantly reduced cell viability and colony formation, accompanied by increased apoptotic rates compared to each treatment alone. Moreover, there was a notable reduction in the expression level of genes associated with cisplatin resistance, particularly ABCG2, MT-2A, GST-pi, and XIAP, in the combined treatment. Wound healing assays indicated that the QU-SLN and cisplatin combination severely impaired OC cell motility compared to cisplatin monotherapy.

Conclusion: QU-SLN and cisplatin combination enhances the therapeutic response in cisplatin-resistant OC cells. By reducing cell proliferation, promoting apoptosis, and downregulating drug resistance genes, QU-SLN might present a promising strategy to improve treatment outcomes for OC patients resistant to cisplatin.

Keywords

nanoparticles

Ovarian Neoplasms

Quercetin