Role of X-linked inhibitor of apoptosis protein in chemoresistance in ovarian cancer: possible involvement of the phosphoinositide-3 kinase/Akt pathway.
Although cisplatin derivatives are first-line chemotherapeutic agents for the treatment of epithelial ovarian cancer, chemoresistance remains a major hurdle to successful therapy and the molecular mechanisms involved are poorly understood. Apoptosis is the cellular underpinning of cisplatin-induced cell death, which is associated with expression of specific "death" genes and down-regulation of "survival" counterparts. The X-linked inhibitor of apoptosis proteins (Xiap), an intracellular anti-apoptotic protein, plays a key role in cell survival by modulating death signaling pathways and is a determinant of cisplatin resistance in ovarian cancer cells in vitro. This review focuses on the role of Xiap and its interactions with the phosphoinositide-3 kinase (PI3K)/Akt cell survival pathway in conferring resistance of ovarian cancer cells to chemotherapeutic agents and discusses potential therapeutic strategies in overcoming chemoresistant ovarian cancer.
Cheng
Jin Q
JQ
Department of Pathology, University of South Florida College of Medicine and H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.
Jiang
Xiuxian
X
Fraser
Michael
M
Li
Ming
M
Dan
Han C
HC
Sun
Mei
M
Tsang
Benjamin K
BK
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000502:physiology / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D051636:X-Linked Inhibitor of Apoptosis Protein
D002945:Cisplatin; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C494918:AKT1 protein, human