Apoptosis and chemoresistance in human ovarian cancer: is Xiap a determinant?
Cisplatin-induced apoptosis in epithelial ovarian cancer cells is in part a consequence of suppressed Xiap expression and upregulation of the Fas/FasL system. Changes in the expression of these 'cell death' and 'cell survival' genes lead to activation of caspase-3, and cleavage of MDM2 and FAK. Failure of cancer cells to maintain a balance in the expression of these genes in favor of apoptotic cell death may be an important factor of chemoresistance. Xiap may be a novel target for gene therapy of human ovarian epithelial cancer and, dependent on P53 status, expression of Xiap antisense alone or in combination with wild-type P53 sense may offer a new approach for the treatment of the chemoresistant cancer.
Li
J
J
Department of Obstetrics and Gynaecology and Department of Cellular and Molecular Medicine, University of Ottawa, Loeb Health Research Institute, The Ottawa Hospital (Civic Campus), Canada.
Sasaki
H
H
Sheng
Y L
YL
Schneiderman
D
D
Xiao
C W
CW
Kotsuji
F
F
Tsang
B K
BK
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology*; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D011506:Proteins / Q000502:physiology*; D051636:X-Linked Inhibitor of Apoptosis Protein
D000970:Antineoplastic Agents; D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D002945:Cisplatin