Alipour Shahriar, Babaei Ghader, Gholizadeh-Ghaleh Aziz Shiva, Abolhasani Somayeh
Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, I.R. Iran.
Student Research Committee, Urmia University of Medical Sciences, Urmia, I.R. Iran.
Res Pharm Sci. 2022 Apr 18;17(3):294-304. doi: 10.4103/1735-5362.343083. eCollection 2022 Jun.
Ovarian cancer is one of the leading causes of cancer mortality in women. Despite the increase in cases of this cancer, the current therapeutic strategy is not effective. This study aimed to investigate the effect of cisplatin (Cis) with alantolactone (ALT) and ZnO nanoparticles (ZnONPs) in inducing apoptosis in SKOV3 ovarian cancer cells line.
To evaluate the viability of SKOV3 cells and determine the IC of Cis, ALT, and ZnONPs, MTT assay was used. Real-time PCR and western blotting were used to evaluate the expression levels of genes (XIAP, cyclin D1, Bcl-2, Bax, and MDM2) and proteins (XIAP, cyclin D1, Bcl-2, Bax), respectively. Also, cellular ROS levels were assessed by fluorimetry.
FINDINGS / RESULTS: Our results showed that ALT and ZnONPs significantly increased the response to Cis in SKOV3 cells compared to the control and this response is remarkably increased in the triple combination (ALT-Cis-ZnONPs). The expression of XIAP, cyclin D1, and Bcl-2 genes and proteins in the groups treated with ALT, Cis, and ZnONPs as a single agent, double and triple combination were significantly reduced compared to the control, while Bax was generally shown an increase. Also, the level of intracellular ROS is higher in the treatment groups than in the control group and the highest increase was observed in the triple combination.
Taken together, our data demonstrated the potential therapeutic approach of using ALT and ZnONPs that may enhance the apoptotic effects of Cis on the SKOV3 cells.
卵巢癌是女性癌症死亡的主要原因之一。尽管这种癌症的病例有所增加,但目前的治疗策略并不有效。本研究旨在探讨顺铂(Cis)与土木香内酯(ALT)和氧化锌纳米颗粒(ZnONPs)联合使用对SKOV3卵巢癌细胞系诱导凋亡的作用。
采用MTT法评估SKOV3细胞的活力,并确定Cis、ALT和ZnONPs的半数抑制浓度(IC)。分别采用实时定量聚合酶链反应(Real-time PCR)和蛋白质印迹法(western blotting)评估基因(XIAP、细胞周期蛋白D1、Bcl-2、Bax和MDM2)和蛋白质(XIAP、细胞周期蛋白D1、Bcl-2、Bax)的表达水平。此外,通过荧光法评估细胞内活性氧(ROS)水平。
我们的结果表明,与对照组相比,ALT和ZnONPs显著增强了SKOV3细胞对Cis的反应,并且三联组合(ALT-Cis-ZnONPs)的这种反应显著增强。与对照组相比,单独使用ALT、Cis和ZnONPs以及双联和三联组合处理组中XIAP、细胞周期蛋白D1和Bcl-2基因及蛋白质的表达均显著降低,而Bax通常呈增加趋势。此外,各治疗组细胞内ROS水平均高于对照组,三联组合中ROS水平升高最为明显。
综上所述,我们的数据表明,使用ALT和ZnONPs可能是一种潜在的治疗方法,可增强Cis对SKOV3细胞的凋亡作用。