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DR5 单克隆抗体 D-6 单独或联合顺铂对 A2780 卵巢癌细胞的凋亡诱导作用。

Apoptosis-inducing effect of the DR5 monoclonal antibody, D-6, alone or in combination with cisplatin, on A2780 ovarian cancer cells.

机构信息

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.

出版信息

Mol Med Rep. 2012 Aug;6(2):316-20. doi: 10.3892/mmr.2012.902. Epub 2012 May 3.

Abstract

Death receptor 5 (DR5) antibody (D-6) is a monoclonal antibody directed against DR5. The aim of this study was to explore the apoptosis-inducing effects of DR5 (D-6), alone or in combination with cisplatin, on A2780 ovarian cancer cells. The cells were treated with various concentrations of cisplatin and/or DR5 (D-6), or a combination of both. For the control group, the cells were treated only with culture medium. Twenty-four hours after the culture, the morphological changes of each group were observed under an inverted microscope. The cell growth inhibition rates were also analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide (MTT) assays, and the apoptosis was analyzed by flow cytometry. Western blotting analysis was used to detect the intracellular reaction. Our results showed that DR5 monoclonal antibody (D-6) was able to induce the apoptosis and increase the cell growth inhibition rates of ovarian cancer cells in a dose-dependent manner, and the effect was enhanced by cisplatin. There were significant morphological changes, a higher cell growth inhibition rate and apoptosis rate and lesser expression of caspase-3, 8, 9 precursors in the cells treated with both cisplatin and DR5 (D-6). The combination treatment of the DR5 monoclonal antibody (D-6) with cisplatin may be a promising treatment for ovarian cancer.

摘要

死亡受体 5(DR5)抗体(D-6)是一种针对 DR5 的单克隆抗体。本研究旨在探讨 DR5(D-6)单独或与顺铂联合应用对 A2780 卵巢癌细胞的诱导凋亡作用。用不同浓度的顺铂和/或 DR5(D-6)或两者联合处理细胞。对照组仅用培养液处理细胞。培养 24 小时后,在倒置显微镜下观察每组细胞的形态变化。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐(MTT)测定分析细胞生长抑制率,并通过流式细胞术分析细胞凋亡。采用 Western blot 分析检测细胞内反应。结果表明,DR5 单克隆抗体(D-6)能够诱导卵巢癌细胞凋亡并呈剂量依赖性增加细胞生长抑制率,且与顺铂联合应用可增强这种作用。与单独应用顺铂或 DR5(D-6)相比,联合应用顺铂和 DR5 单克隆抗体(D-6)可使细胞出现明显的形态学变化,细胞生长抑制率和凋亡率更高,caspase-3、8、9 前体表达水平更低。DR5 单克隆抗体(D-6)联合顺铂治疗可能是一种有前途的卵巢癌治疗方法。

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