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刺蕊草酮对卵巢癌细胞系中肿瘤抑制基因的表达、细胞周期及细胞凋亡的影响评估

evaluation of the pogostone effects on the expression of and tumor suppressor genes, cell cycle, and apoptosis in ovarian cancer cell line.

作者信息

Homayoun Mansour, Sajedi Nayereh, Soleimani Mitra

机构信息

Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

Department of Anatomical Sciences, Qom Branch, Islamic Azad University, Qom, I.R. Iran.

出版信息

Res Pharm Sci. 2022 Jan 15;17(2):164-175. doi: 10.4103/1735-5362.335175. eCollection 2022 Apr.

DOI:10.4103/1735-5362.335175
PMID:35280836
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8860107/
Abstract

BACKGROUND AND PURPOSE

Ovarian cancer is one of the most dangerous cancers among women. Pogostone has anticancer effects and is rich in polyphenol compounds. In the present study, we investigated the effects of pogostone on ovarian cancer cell lines (OVCAR-3).

EXPERIMENTAL APPROACH

OVCAR-3 cells were treated with pogostone at IC(90 μg/mL) for 24 and 48 h. Cell viability and apoptotic rate in the cells were measured using MTT assay and flow cytometry. Real-time PCR was used to determine the expression of genes involved in the cell cycle and apoptosis. The expression of caspase-3 (CASP3) protein was evaluated by the CASP3 assay.

FINDINGS/RESULTS: Treatment of OVCAR-3 cells with pogostone increased the expression levels of phosphatase and tensin homologue deleted on chromosome ten () and Dapper antagonist of catenin-1 () tumor suppressor genes, as well as the apoptotic genes , , and . Moreover, the ratio of the expressed associated X ()/ genes, as pro- and anti-apoptotic genes, was increased. The expression levels of the genes related to the cell cycle progression including cyclin D1 () and cyclin- dependent kinase 4 () were inhibited. The data obtained from flow cytometry indicated that pogostone induced cell apoptosis in 24 and 48 pogostone groups. The CASP3 colorimetric assay revealed that pogostone increased the expression of CASP3 protein in the treated groups.

CONCLUSION AND IMPLICATION

Pogostone, by inducing the expression of and tumor suppressor genes and regulation of downstream genes may decrease cell proliferation and increase the rate of apoptosis in OVCAR-3.

摘要

背景与目的

卵巢癌是女性中最危险的癌症之一。广藿香酮具有抗癌作用,且富含多酚类化合物。在本研究中,我们调查了广藿香酮对卵巢癌细胞系(OVCAR-3)的影响。

实验方法

用广藿香酮(IC为90μg/mL)处理OVCAR-3细胞24小时和48小时。使用MTT法和流式细胞术测量细胞活力和细胞凋亡率。采用实时定量PCR法测定参与细胞周期和凋亡的基因表达。通过半胱天冬酶-3(CASP3)检测评估CASP3蛋白的表达。

研究结果

用广藿香酮处理OVCAR-3细胞可增加第10号染色体上缺失的磷酸酶和张力蛋白同源物(PTEN)以及连环蛋白-1的拮抗剂(DACT1)肿瘤抑制基因的表达水平,以及凋亡基因BAX、BIM和PUMA的表达水平。此外,作为促凋亡基因和抗凋亡基因的Bax相关X蛋白(BAX)/Bcl-2基因的表达比例增加。抑制了包括细胞周期蛋白D1(CCND1)和细胞周期蛋白依赖性激酶4(CDK4)在内的与细胞周期进程相关基因的表达水平。流式细胞术获得的数据表明,广藿香酮在24小时和48小时的广藿香酮处理组中诱导细胞凋亡。CASP3比色法显示,广藿香酮增加了处理组中CASP3蛋白的表达。

结论与意义

广藿香酮通过诱导PTEN和DACT1肿瘤抑制基因的表达以及下游基因的调控,可能会降低OVCAR-3细胞的增殖并增加凋亡率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2776/8860107/09c02ffda79d/RPS-17-164-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2776/8860107/7274ebd9534a/RPS-17-164-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2776/8860107/c0423c2812e0/RPS-17-164-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2776/8860107/0a9d417a4d17/RPS-17-164-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2776/8860107/a3f3ca1b7622/RPS-17-164-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2776/8860107/5b574120abe4/RPS-17-164-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2776/8860107/09c02ffda79d/RPS-17-164-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2776/8860107/7274ebd9534a/RPS-17-164-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2776/8860107/c0423c2812e0/RPS-17-164-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2776/8860107/0a9d417a4d17/RPS-17-164-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2776/8860107/a3f3ca1b7622/RPS-17-164-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2776/8860107/5b574120abe4/RPS-17-164-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2776/8860107/09c02ffda79d/RPS-17-164-g006.jpg

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