Masoudi Ehsan, Soleimani Mitra, Zarinfard Giti, Homayoun Mansour, Bakhtiari Mohammad
Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Anatomical Sciences, School of Medicine, Behbahan University of Medical Sciences, Behbahan, Iran.
Res Pharm Sci. 2024 Feb 6;19(1):53-63. doi: 10.4103/1735-5362.394820. eCollection 2024 Feb.
Ovarian cancer is the deadliest gynecological cancer. Bromodomain and extra terminal domain (BET) proteins play major roles in the regulation of gene expression at the epigenetic level. Jun Qi (JQ1) is a potent inhibitor of BET proteins. Regarding the short half-life and poor pharmacokinetic profile, JQ1 was loaded into newly developed nano-carriers. Chitosan nanoparticles are one of the best and potential polymers in cancer treatment. The present study aimed to build chitosan-JQl nanoparticles (Ch-J-NPs), treat OVCAR-3 cells with Ch-J-NPs, and evaluate the effects of these nanoparticles on cell cycle and apoptosis-associated genes.
Ch-J-NPs were synthesized and characterized. The size and morphology of Ch-J-NPs were defined by DLS and FE-SEM techniques. OVCAR-3 cells were cultured and treated with Ch-J-NPs. Then, IC was measured using MTT assay. The groups were defined and cells were treated with IC concentration of Ch-J-NPs, for 48 h. Finally, cells in different groups were assessed for the expression of genes of interest using quantitative RT-PCR.
FINDINGS/RESULTS: IC values for Ch-J-NPs were 5.625 μg/mL. RT-PCR results demonstrated that the expression of genes associated with cell cycle activity (c-MYC, hTERT, CDK1, CDK4, and CDK6) was significantly decreased following treatment of cancer cells with Ch-J-NPs. Conversely, the expression of caspase-3, and caspase-9 significantly increased. BAX (pro-apoptotic) to BCL2 (anti-apoptotic) expression ratio, also increased significantly after treatment of cells with Ch-J-NPs.
Ch-J-NPs showed significant anti-cell cyclic and apoptotic effects on OVCAR-3 cells.
卵巢癌是最致命的妇科癌症。溴结构域和额外末端结构域（BET）蛋白在表观遗传水平的基因表达调控中起主要作用。JQ1是一种有效的BET蛋白抑制剂。鉴于其半衰期短和药代动力学特性不佳，JQ1被载入新开发的纳米载体中。壳聚糖纳米颗粒是癌症治疗中最优良且有潜力的聚合物之一。本研究旨在制备壳聚糖-JQ1纳米颗粒（Ch-J-NPs），用Ch-J-NPs处理卵巢癌细胞系OVCAR-3，并评估这些纳米颗粒对细胞周期和凋亡相关基因的影响。
合成并表征Ch-J-NPs。通过动态光散射（DLS）和场发射扫描电子显微镜（FE-SEM）技术确定Ch-J-NPs的大小和形态。培养OVCAR-3细胞并用Ch-J-NPs处理。然后，使用MTT法测定半数抑制浓度（IC）。定义分组，并用Ch-J-NPs的IC浓度处理细胞48小时。最后，使用定量逆转录聚合酶链反应（qRT-PCR）评估不同组细胞中目的基因的表达。
Ch-J-NPs的IC值为5.625μg/mL。逆转录聚合酶链反应（RT-PCR）结果表明，用Ch-J-NPs处理癌细胞后，与细胞周期活性相关的基因（c-MYC、人端粒酶逆转录酶（hTERT）、细胞周期蛋白依赖性激酶1（CDK1）、细胞周期蛋白依赖性激酶4（CDK4）和细胞周期蛋白依赖性激酶6（CDK6））的表达显著降低。相反，半胱天冬酶-3和半胱天冬酶-9的表达显著增加。在用Ch-J-NPs处理细胞后，促凋亡蛋白BAX与抗凋亡蛋白BCL2的表达比值也显著增加。
Ch-J-NPs对OVCAR-3细胞显示出显著的抗细胞周期和凋亡作用。
