Aurora kinase inhibitor VE 465 synergistically enhances cytotoxicity of carboplatin in ovarian cancer cells through induction of apoptosis and downregulation of histone 3
Authors: Siqing Fu, Yanfang li, Jie Huang, Tao Liu, Zhen Hong, Aiping Chen, Robert C. Bast, John J. Kavanagh, David M. Gershenson, Anil K. Sood and Wei Hu
Department of Investigational Cancer Therapeutics; The University of Texas MD Anderson Cancer Center; Houston, TX USA
Yanfang li
Department of Gynecologic Oncology and Reproductive Medicine; The University of Texas MD Anderson Cancer Center; Houston, TX USA; Department of Gynecologic Oncology; The Sun Yat-sen University Cancer Center; Guangzhou, China
Jie Huang
Department of Gynecologic Oncology and Reproductive Medicine; The University of Texas MD Anderson Cancer Center; Houston, TX USA
Tao Liu
Department of Gynecologic Oncology and Reproductive Medicine; The University of Texas MD Anderson Cancer Center; Houston, TX USA
Zhen Hong
Department of Gynecologic Oncology and Reproductive Medicine; The University of Texas MD Anderson Cancer Center; Houston, TX USA; Department of Gynecology; Beijing Cancer Hospital; Beijing, China
Aiping Chen
Department of Gynecologic Oncology and Reproductive Medicine; The University of Texas MD Anderson Cancer Center; Houston, TX USA
Robert C. Bast
Department of Experimental Therapeutics; The University of Texas MD Anderson Cancer Center; Houston, TX USA
John J. Kavanagh
Department of Gynecologic Oncology and Reproductive Medicine; The University of Texas MD Anderson Cancer Center; Houston, TX USA
David M. Gershenson
Department of Gynecologic Oncology and Reproductive Medicine; The University of Texas MD Anderson Cancer Center; Houston, TX USA
Anil K. Sood
Department of Gynecologic Oncology and Reproductive Medicine; The University of Texas MD Anderson Cancer Center; Houston, TX USA; Department of Cancer Biology; The University of Texas MD Anderson Cancer Center; Houston, TX USA; Center for RNAi and Mon-coding RNA; The University of Texas MD Anderson Cancer Center; Houston, TX USA
Wei Hu
Corresponding author: weihu@mdanderson.org
Department of Gynecologic Oncology and Reproductive Medicine; The University of Texas MD Anderson Cancer Center; Houston, TX USA
Abstract:
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.
Received: April 10, 2012; Accepted: June 6, 2012; Published Online: August 16, 2012
Purchase or Subscribe
