Shamsi Masoumeh, Babaahmadi-Rezaei Hossien, Khedri Azam, Hatami Mahdi, Rashidi Mojtaba
Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Iran Biomed J. 2025 Jan 1;29(1 & 2):20-35. doi: 10.61186/ibj.4543.
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.
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.
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.
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.
卵巢癌（OC）仍然是妇科癌症中导致死亡的主要原因，主要是因为对铂类化疗药物，尤其是顺铂产生耐药性。本研究调查了载有槲皮素（QU）的固体脂质纳米粒（SLNs）解决OC细胞顺铂耐药性的潜力。
在体外对顺铂耐药的SK-OV-3和顺铂敏感的A2780s人OC细胞系评估QU-SLN的疗效。包括细胞毒性、细胞活力、克隆形成、流式细胞术、定量逆转录聚合酶链反应和伤口愈合试验在内的各种试验，评估了QU和QU-SLN与顺铂联合对细胞活力、凋亡、与顺铂耐药相关的基因表达水平以及细胞迁移的综合影响。
与单独的每种治疗相比，将QU-SLN与顺铂联合使用可显著降低细胞活力和集落形成，同时凋亡率增加。此外，联合治疗中与顺铂耐药相关的基因，特别是ABCG2、MT-2A、GST-pi和XIAP的表达水平显著降低。伤口愈合试验表明，与顺铂单药治疗相比，QU-SLN和顺铂联合使用严重损害了OC细胞的运动能力。
QU-SLN与顺铂联合可增强对顺铂耐药的OC细胞的治疗反应。通过减少细胞增殖、促进凋亡和下调耐药基因，QU-SLN可能是一种改善对顺铂耐药的OC患者治疗效果的有前景的策略。
