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

Zhao, Wen-Jing; Deng, Bo-Ya; Wang, Xue-Mei; Miao, Yuan; Wang, Jian-Nan

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자료유형: 학술저널

저자정보: Zhao, Wen-Jing (Department of Medical Ultrasonics, The First Affiliated Hospital of China Medical University) Deng, Bo-Ya (Department of Gynecology, The First Affiliated Hospital of China Medical University) Wang, Xue-Mei (Department of Medical Ultrasonics, The First Affiliated Hospital of China Medical University) Miao, Yuan (Department of Pathology, The First Affiliated Hospital of China Medical University) Wang, Jian-Nan (Department of Medical Ultrasonics, The First Affiliated Hospital of China Medical University)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제16권 제6호

발행연도: 2015.1

수록면: 2,453 - 2,458 (6page)

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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. Methods and 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 antiproliferative 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.

#Epithelial ovarian cancer cells #XAF1 #invasion #apoptosis #cisplatin sensitivity

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Zhao, Wen-Jing

소속기관 Department of Medical Ultrasonics, The First Affiliated Hospital of China Medical University