Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
Mol Med Rep. 2012 Aug;6(2):316-20. doi: 10.3892/mmr.2012.902. Epub 2012 May 3.
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.
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。