Gametogenesis Research Center, Kashan University of Medical Science, Kashan, Iran.
Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Cell Biol Toxicol. 2019 Jun;35(3):247-266. doi: 10.1007/s10565-018-09450-8. Epub 2018 Nov 26.
Drug resistance remains a major challenge in the treatment of patients with ovarian cancer. Therefore, the development of new anticancer drugs is a clinical priority to develop more effective therapies. New approaches to improve clinical outcomes and limit the toxicity of anticancer drugs focus on chemoprevention. The aim of this study was to determine the effects of dendrosomal nanocurcumin (DNC) and oxaliplatin (Oxa) and their combination on cell death and apoptosis induction in human ovarian carcinoma cell lines analyzed by MTT assay and flow cytometry, respectively. The synergism effect of Oxa and DNC was analyzed using the equation derived from Chou and Talalay. In addition, real-time PCR was used to measure the effect of this combination on the expression levels of long non-coding RNAs with different expression in ovarian cancer and normal ovaries. Our data showed that the effect of DNC on cell death is more than curcumin alone in the same concentration. The greatest cell death effect was observed in combination of Oxa with DNC, while Oxa was added first, followed by DNC at 4 h interval (0/4 h). The findings indicated that DNC induced apoptosis significantly in both cell lines as compared to control groups; however, combination of both agents had no significant effect in apoptosis induction. In addition, combination of both agents significantly affects the relative expression of long non-coding RNAs investigated in the study as compared with mono therapy.
耐药性仍然是卵巢癌患者治疗的主要挑战。因此,开发新的抗癌药物是临床优先事项,以开发更有效的治疗方法。改善临床结果和限制抗癌药物毒性的新方法侧重于化学预防。本研究的目的是通过 MTT 分析分别确定树状纳米姜黄素 (DNC) 和奥沙利铂 (Oxa) 及其组合对人卵巢癌细胞系细胞死亡和凋亡诱导的影响,通过流式细胞术进行分析。使用 Chou 和 Talalay 推导的方程分析 Oxa 和 DNC 的协同作用。此外,实时 PCR 用于测量该组合对卵巢癌和正常卵巢中不同表达的长非编码 RNA 表达水平的影响。我们的数据表明,在相同浓度下,DNC 对细胞死亡的影响大于单独使用姜黄素。在奥沙利铂与 DNC 联合使用时观察到最大的细胞死亡效果,而奥沙利铂首先添加,然后在 4 小时间隔(0/4 小时)添加 DNC。研究结果表明,与对照组相比,DNC 可显著诱导两种细胞系中的细胞凋亡;然而,与单药治疗相比,联合使用两种药物对凋亡诱导没有显著影响。此外,与单药治疗相比,联合使用两种药物会显著影响研究中调查的长非编码 RNA 的相对表达。