Downregulation of XIAP expression in ovarian cancer cells induces cell death in vitro and in vivo
Article first published online: 20 NOV 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 122, Issue 6, pages 1430–1434, 15 March 2008
How to Cite
Shaw, T. J., Lacasse, E. C., Durkin, J. P. and Vanderhyden, B. C. (2008), Downregulation of XIAP expression in ovarian cancer cells induces cell death in vitro and in vivo. Int. J. Cancer, 122: 1430–1434. doi: 10.1002/ijc.23278
- Issue published online: 21 JAN 2008
- Article first published online: 20 NOV 2007
- Manuscript Accepted: 21 SEP 2007
- Manuscript Received: 1 DEC 2006
- National Cancer Institute of Canada
- Canadian Institutes of Health Research
A hallmark of cancer cells is an ability to evade apoptosis. Overexpression and/or activating mutations of prosurvival molecules such as the X-linked inhibitor of apoptosis (XIAP) contribute to this inappropriate cell survival. Our objectives were to investigate the effects of downregulation of XIAP in ovarian cancer cells in vitro and in vivo using the clinical candidate antisense oligonucleotide against XIAP, AEG35156 (AS XIAP). Three ovarian cancer cell lines were transfected with AS XIAP in vitro, and the effects on cell survival were assessed. Downregulation of XIAP resulted in significant apoptosis. To investigate the in vivo efficacy of AS XIAP, CD-1 nude mice were xenografted intraperitoneally with A2780-cp cells, treated with intraperitoneal AS XIAP and evaluated for survival time and tumor histology. Mice treated with 10 mg/kg/day AS XIAP showed a significant improvement in survival time compared to animals treated with control oligonucleotides. Histological analysis of the tumors showed significantly fewer viable cells in the AS XIAP-treated tumors. Downregulation of XIAP expression in ovarian cancer cells resulted in apoptosis in vitro and a prolonged survival time of ovarian cancer-bearing mice, which indicate that XIAP may be a valuable therapeutic target in ovarian cancers, and supports the ongoing clinical investigation of AEG35156. © 2007 Wiley-Liss, Inc.