DOI QR코드

DOI QR Code

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 (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)
  • 발행 : 2015.04.03

초록

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.

키워드

참고문헌

  1. Arikan SK, Kasap B, Yetimalar H, et al (2014). Impact of prognostic factors on survival rates in patients with ovarian carcinoma. Asian Pac J Cancer Prev, 15, 6087-94. https://doi.org/10.7314/APJCP.2014.15.15.6087
  2. Byun DS, Cho K, Ryu BK, et al (2003). Hypermethylation of XIAP-associated factor 1, a putative tumor suppressor gene from the 17p13.2 locus, in human gastric adenocarcinomas. Cancer Res, 63, 7068-75.
  3. Chen XY, He QY, Guo MZ (2012). XAF1 is frequently methylated in human esophageal cancer. World J Gastroenterol, 18, 2844-9. https://doi.org/10.3748/wjg.v18.i22.2844
  4. Chen YB, Shu J, Yang WT, et al (2011). XAF1 as a prognostic biomarker and therapeutic target in squamous cell lung cancer. Chin Med J, 124, 3238-43.
  5. Kempkensteffen C, Fritzsche FR, Johannsen M, et al (2009). Down-regulation of the pro-apoptotic XIAP associated factor-1 (XAF1) during progression of clear-cell renal cancer. BMC Cancer, 9, 276. https://doi.org/10.1186/1471-2407-9-276
  6. Kempkensteffen C, Hinz S, Schrader M, et al (2007). Gene expression and promoter methylation of the XIAP-associated Factor 1 in renal cell carcinomas: correlations with pathology and outcome. Cancer Lett, 254, 227-35. https://doi.org/10.1016/j.canlet.2007.03.006
  7. Kim MA, Lee HE, Lee HS, et al (2011). Expression of apoptosis-related proteins and its clinical implication in surgically resected gastric carcinoma. Virchows Arch, 459, 503-10. https://doi.org/10.1007/s00428-011-1150-6
  8. LeBleu VS, Taduri G, O'Connell J, et al (2013). Origin and function of myofibroblasts in kidney fibrosis. Nat Med, 19, 1047-53. https://doi.org/10.1038/nm.3218
  9. Li G, Chang H, Zhai YP, et al (2013). Targeted silencing of inhibitors of apoptosis proteins with siRNAs: a potential anti-cancer strategy for hepatocellular carcinoma. Asian Pac J Cancer Prev, 14, 4943-52.
  10. Li XQ, Ke XZ, Wang YM (2012). Treatment of malignant melanoma by downregulation of XIAP and overexpression of TRAIL with a conditionally replicating oncolytic adenovirus. Asian Pac J Cancer Prev, 13, 1471-6. https://doi.org/10.7314/APJCP.2012.13.4.1471
  11. Ling ZQ, Lv P, Lu XX, et al (2013). Circulating methylated DNA Indicates poor prognosis for gastric cancer. PLoS One, 8, 67195. https://doi.org/10.1371/journal.pone.0067195
  12. Liston P, Fong WG, Kelly NL, et al (2001). Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. Nat Cell Biol, 3, 128-33. https://doi.org/10.1038/35055027
  13. Ma B, Wang Y, Zhou X, et al (2014). Synergistic suppression effect on tumor growth of hepatocellular carcinoma by combining oncolytic adenovirus carrying XAF1 with cisplatin. J Cancer Res Clin Oncol, 141, 419-29
  14. Ma TL, Ni PH, Zhong J, et al (2005). Low expression of XIAP-associated factor 1 in human colorectal cancers. Chin J Dig Dis, 6, 10-4. https://doi.org/10.1111/j.1443-9573.2005.00180.x
  15. Mhawech-Fauceglia P, Yan L, Sharifian M, et al (2014). Stromal expression of fibroblast activation protein alpha (FAP) predicts platinum resistance and shorter recurrence in patients with epithelial ovarian cancer. Cancer Microenviron. [Epub ahead of print]
  16. Murphy TM, Perry AS, Lawler M (2008). The emergence of DNA methylation as a key modulator of aberrant cell death in prostate cancer. Endocr Relat Cancer, 15, 11-25. https://doi.org/10.1677/ERC-07-0208
  17. Ng KC, Campos EI, Martinka M, et al (2004). XAF1 expression is significantly reduced in human melanoma. J Invest Dermatol, 123, 1127-34. https://doi.org/10.1111/j.0022-202X.2004.23467.x
  18. Qi R, Gu J, Zhang Z, et al (2007). Potent antitumor efficacy of XAF1 delivered by conditionally replicative adenovirus vector via caspase-independent apoptosis. Cancer Gene Ther, 14, 82-90. https://doi.org/10.1038/sj.cgt.7700992
  19. Qiao L, Gu Q, Dai Y, et al (2008). XIAP-associated factor 1 (XAF1) suppresses angiogenesis in mouse endothelial cells. Tumour Biol, 29, 122-9. https://doi.org/10.1159/000137831
  20. Rai B, Bansal A, Patel FD, et al (2014). Radiotherapy for ovarian cancers - redefining the role. Asian Pac J Cancer Prev, 15, 4759-63. https://doi.org/10.7314/APJCP.2014.15.12.4759
  21. Russell S, Duquette M, Liu J, et al (2014). Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian cancer. FASEB J, 29, 576-88
  22. Sakemi R, Yano H, Ogasawara S, et al (2007). X-linked inhibitor of apoptosis (XIAP) and XIAP-associated factor-1 expressions and their relationship to apoptosis in human hepatocellular carcinoma and non-cancerous liver tissues. Oncol Rep, 18, 65-70.
  23. Shibata T, Mahotka C, Wethkamp N, et al (2007). Disturbed expression of the apoptosis regulators XIAP, XAF1, and Smac/DIABLO in gastric adenocarcinomas. Diagn Mol Pathol, 16, 1-8. https://doi.org/10.1097/01.pdm.0000213471.92925.51
  24. Shibata T, Noguchi T, Takeno S, et al (2008). Disturbed XIAP and XAF1 expression balance is an independent prognostic factor in gastric adenocarcinomas. Ann Surg Oncol, 15, 3579-87. https://doi.org/10.1245/s10434-008-0062-4
  25. Siegel R, Naishadham D, Jemal A (2013). Cancer statistics, 2013. CA Cancer J Clin, 63, 11-30. https://doi.org/10.3322/caac.21166
  26. Wang J, Peng Y, Sun YW, et al (2006). All-trans retinoic acid induces XAF1 expression through an interferon regulatory factor-1 element in colon cancer. Gastroenterology, 130, 747-58. https://doi.org/10.1053/j.gastro.2005.12.017
  27. Wang Y, Mao H, Hao Q, et al (2012). Association of expression of XIAP-associated factor 1 (XAF1) with clinicopathologic factors, overall survival, microvessel density and cisplatin-resistance in ovarian cancer. Regul Pept, 178, 36-42. https://doi.org/10.1016/j.regpep.2012.06.005
  28. Wu LM, Zhang F, Zhou L, et al (2010). Predictive value of CpG island methylator phenotype for tumor recurrence in hepatitis B virus-associated hepatocellular carcinoma following liver transplantation. BMC Cancer, 10, 399. https://doi.org/10.1186/1471-2407-10-399
  29. Yang WT, Chen DL, Zhang FQ, et al (2014). Experimental study on inhibition effects of the XAF1 gene against lung cancer cell proliferation. Asian Pac J Cancer Prev, 15, 7825-9. https://doi.org/10.7314/APJCP.2014.15.18.7825
  30. Yin DT, Chen G, Li HQ, et al (2012). Relationship between methylation status of promoter and expression of XAF1 gene in papillary thyroid carcinoma. Zhonghua Yi Xue Za Zhi, 92, 1967-70.
  31. Zhang F, Wu LM, Zhou L, et al (2008). Predictive value of expression and promoter hypermethylation of XAF1 in hepatitis B virus-associated hepatocellular carcinoma treated with transplantation. Ann Surg Oncol, 15, 3494-502. https://doi.org/10.1245/s10434-008-0146-1
  32. Zhu L, Cheng X, Ding Y, et al (2014a). Bone marrow-derived myofibroblasts promote colon tumorigenesis through the IL-6/JAK2/STAT3 pathway. Cancer Lett, 343, 80-9. https://doi.org/10.1016/j.canlet.2013.09.017
  33. Zhu LM, Shi DM, Dai Q, et al (2014b). Tumor suppressor XAF1 induces apoptosis, inhibits angiogenesis and inhibits tumor growth in hepatocellular carcinoma. Oncotarget, 5, 5403-15. https://doi.org/10.18632/oncotarget.2114

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