Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cancer Biol Ther. 2012 Sep;13(11):1034-41. doi: 10.4161/cbt.21045. Epub 2012 Aug 16.
Aurora kinases are essential for regulation of chromosome segregation and cytokinesis during mitosis and play a role in growth and progression of human tumors, including ovarian cancer. Aurora A and Aurora B are frequently overexpressed in high-grade and low-grade ovarian cancers. Targeting Aurora kinases has great potential for improving the efficacy of chemotherapies of ovarian cancer. In this study, we investigated whether the Aurora kinase inhibitor, VE 465, can enhance the anti-tumor activity of carboplatin in human ovarian cancer cells. The antitumor activity of VE 465 was tested by MTT proliferative assay in multiple established human epithelial ovarian cancer cell lines of varying p53 status. VE 465 and carboplatin had a synergistic effect on cell viability in both platinum-sensitive and -resistant ovarian cancers. The growth-inhibitory effect was accompanied by reduction in expression of histone 3 and an increase in apoptosis. We conclude that VE 465 enhances the efficacy of carboplatin agents in ovarian carcinoma.
极光激酶对于有丝分裂过程中染色体分离和胞质分裂的调节至关重要，并在包括卵巢癌在内的人类肿瘤的生长和进展中发挥作用。Aurora A 和 Aurora B 在高级别和低级别卵巢癌中经常过度表达。靶向 Aurora 激酶具有提高卵巢癌化疗疗效的巨大潜力。在这项研究中，我们研究了 Aurora 激酶抑制剂 VE-465 是否可以增强卡铂在人卵巢癌细胞中的抗肿瘤活性。通过 MTT 增殖试验在多种不同 p53 状态的已建立的人上皮性卵巢癌细胞系中测试了 VE-465 的抗肿瘤活性。VE-465 和卡铂对铂敏感和耐药的卵巢癌的细胞活力均具有协同作用。生长抑制作用伴随着组蛋白 3 表达的减少和凋亡的增加。我们得出结论，VE-465 增强了卡铂类药物在卵巢癌中的疗效。
