title: XIAP associated factor 1 (XAF1) represses expression of X-linked inhibitor of apoptosis protein (XIAP) and regulates invasion, cell cycle, apoptosis, and cisplatin sensitivity of ovarian carcinoma cells.
abstract: BACKGROUND
  X-linked inhibitor of apoptosis protein (XIAP) associated factor 1 (XAF1) exhibits aberrantly low or absent expression in various human malignancies, closely associated with anti-apoptosis and overgrowth of cancer cells. However, limited attention has been directed towards the contribution of XAF1 to invasion, apoptosis, and cisplatin (DDP)-resistance of epithelial ovarian cancer (EOC) cells. This study aimed to evaluate the potential effects of XAF1 on invasion, cell cycle, apoptosis, and cisplatin-resistance by overexpressing XAF1 in SKOV-3 and SKOV-3/DDP cells.
  
  
  RESULTS
  The pEGFP-C1-XAF1 plasmid was transfected into SKOV-3 and SKOV-3/DDP cells, and the expression of XAF1 at both mRNA and protein levels was analyzed by reverse transcription-PCR and Western blotting. Overexpression of XAF1 suppressed XIAP expression in both SKOV-3 and SKOV-3/DDP cells. Transwell invasion assays demonstrated that XAF1 exerted a strong anti-invasive effect in XAF1-overexpressing cells. Moreover, flow cytometry analysis revealed that XAF1 overexpression arrested the cell cycle at G0/G1 phase, and cell apoptosis analysis showed that overexpression of XAF1 enhanced apoptosis of SKOV-3 and SKOV-3/DDP cells apparently by activating caspase-9 and caspase-3. Furthermore, MTT assay confirmed a dose-dependent inhibitory effect of cisplatin in the tested tumor cells, and overexpression of XAF1 increased the sensitivity of SKOV-3 and SKOV-3/DDP cells to cisplatin-mediated anti- proliferative effects.
  
  
  CONCLUSIONS
  In summary, our data indicated that overexpression of XAF1 could suppress XIAP expression, inhibit invasion, arrest cell cycle, promote apoptosis, and confer cisplatin-sensitivity in SKOV-3 and SKOV-3/DDP cells. Therefore, XAF1 may be further assessed as a potential target for the treatment of both cisplatin-resistant and non-resistant EOCs.
authors.affiliation: Department of Medical Ultrasonics, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China E-mail : xuemeiwangx@163.com.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Zhao
authors.forename: Bo-Ya
authors.initials: BY
authors.lastname: Deng
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Miao
authors.forename: Jian-Nan
authors.initials: JN
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D051636:X-Linked Inhibitor of Apoptosis Protein; C417551:XAF1 protein, human; C496866:XIAP protein, human; D002945:Cisplatin