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

Background: X-linked inhibitor of apoptosis protein (XIAP) associated factor 1 (XAF1) exhibits aberrantlylow or absent expression in various human malignancies, closely associated with anti-apoptosis and overgrowthof 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 evaluatethe potential effects of XAF1 on invasion, cell cycle, apoptosis, and cisplatin-resistance by overexpressing XAF1in SKOV-3 and SKOV-3/DDP cells. Methods and
Results: The pEGFP-C1-XAF1 plasmid was transfected intoSKOV-3 and SKOV-3/DDP cells, and the expression of XAF1 at both mRNA and protein levels was analyzedby reverse transcription-PCR and Western blotting. Overexpression of XAF1 suppressed XIAP expression inboth SKOV-3 and SKOV-3/DDP cells. Transwell invasion assays demonstrated that XAF1 exerted a stronganti-invasive effect in XAF1-overexpressing cells. Moreover, flow cytometry analysis revealed that XAF1overexpression arrested the cell cycle at G0/G1 phase, and cell apoptosis analysis showed that overexpression ofXAF1 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, andoverexpression of XAF1 increased the sensitivity of SKOV-3 and SKOV-3/DDP cells to cisplatin-mediated antiproliferativeeffects.
Conclusions: In summary, our data indicated that overexpression of XAF1 could suppressXIAP expression, inhibit invasion, arrest cell cycle, promote apoptosis, and confer cisplatin-sensitivity in SKOV-3and SKOV-3/DDP cells. Therefore, XAF1 may be further assessed as a potential target for the treatment of bothcisplatin-resistant and non-resistant EOCs