Patel Binita, Patel Shanaya, Modi Foram, Patel Aditi, Gelat Brijesh, Tanavde Vivek, Vasavada Abhay, Johar Kaid
Department of Life Sciences, School of Sciences, Gujarat University, Ahmedabad, 380009, Gujarat, India.
Division of Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Central Campus, Ahmedabad, 380009, Gujarat, India.
Sci Rep. 2024 Dec 28;14(1):30672. doi: 10.1038/s41598-024-74277-9.
Ovarian cancer is known to be a challenging disease to detect at an early stage and is a major cause of death among women. The current treatment for ovarian cancer typically involves a combination of surgery and the use of drugs such as platinum-based cytotoxic agents, anti-angiogenic drugs, etc. However, current treatment methods are not always effective in preventing the recurrence of ovarian cancer. As a result, the treatments administered after a relapse need to be more aggressive, leading to increased toxicity and drug resistance. To address this issue, researchers are exploring the potential of combining existing anticancer agents with novel or repurposed drugs to reduce the side effects and improve the effectiveness of treatment. In this study, we have investigated the use of rosiglitazone, a well-known anti-diabetic drug, in combination with the chemotherapeutic drug, paclitaxel for the prevention of ovarian cancer. The study utilized the SKOV-3 ovarian cancer cell line to assess the effects of this combination treatment. The results of the study showed that the combination of paclitaxel with rosiglitazone inhibited cell proliferation at much lower concentrations of paclitaxel as compared to paclitaxel alone. The combined treatment also induced cell cycle arrest at the G2/M phase and increased apoptosis by altering the mitochondrial membrane potential of the cells. Additionally, the combination treatment activated the PPAR-γ pathway and downregulated expression of genes associated with cancer stemness, such as NANOG, OCT4, and EHF. Furthermore, the CAM assay substantiated the anti-angiogenic potential of the synergistic treatment of paclitaxel and rosiglitazone. The findings of the study suggest that repurposing rosiglitazone as an anticancer agent in combination with paclitaxel has immense potential to target cancer cell cycle progression and apoptosis, making it a promising therapeutic approach for sensitizing chemo-resistant population of ovarian cancer cells.
卵巢癌是一种在早期难以检测的具有挑战性的疾病,也是女性死亡的主要原因。目前卵巢癌的治疗通常包括手术以及使用铂类细胞毒性药物、抗血管生成药物等。然而,目前的治疗方法在预防卵巢癌复发方面并不总是有效。因此,复发后进行的治疗需要更积极,这导致毒性增加和耐药性。为了解决这个问题,研究人员正在探索将现有抗癌药物与新型或重新利用的药物联合使用的潜力,以减少副作用并提高治疗效果。在这项研究中,我们研究了著名的抗糖尿病药物罗格列酮与化疗药物紫杉醇联合用于预防卵巢癌的情况。该研究利用SKOV-3卵巢癌细胞系评估这种联合治疗的效果。研究结果表明,与单独使用紫杉醇相比,紫杉醇与罗格列酮联合使用在低得多的紫杉醇浓度下就能抑制细胞增殖。联合治疗还诱导细胞周期停滞在G2/M期,并通过改变细胞的线粒体膜电位增加细胞凋亡。此外,联合治疗激活了PPAR-γ途径,并下调了与癌症干性相关的基因如NANOG、OCT4和EHF的表达。此外,鸡胚绒毛尿囊膜试验证实了紫杉醇和罗格列酮联合治疗的抗血管生成潜力。该研究结果表明,将罗格列酮重新用作抗癌药物与紫杉醇联合使用,在靶向癌细胞周期进程和细胞凋亡方面具有巨大潜力,使其成为使卵巢癌化疗耐药细胞群体敏感化的一种有前景的治疗方法。