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Downregulation of XIAP expression induces apoptosis and enhances chemotherapeutic sensitivity in human gastric cancer cells

Cancer Gene Therapy volume 12, pages 509–514 (2005)Cite this article

Abstract

X-linked inhibitor of apoptosis (XIAP) is the most potent member of the inhibitor of apoptosis protein (IAP) gene family in terms of its ability to inhibit caspases and suppress apoptosis. Recent evidence has suggested that XIAP is a key determinant in chemoresistance of cancer cells. To explore a novel approach for ameliorating chemotherapy of gastric cancer, the antisense expression vector for the XIAP gene was constructed and transferred into gastric cancer cell lines, MKN-45 (wild-type p53) and MKN-28 (mutant-type p53). This transfer resulted in significant downregulation of XIAP expression, decreased in vitro cell viabilities, and induced apoptosis. In transferred cells, inactive caspase-3 precursors were cleaved into the active subunits (p20 and p17) during apoptosis induced by downregulation of XIAP. The inhibitory effects of cisplatin and mitomycin C on the growth of XIAP downregulated cancer cells were significantly enhanced. In addition, this process occurred only in wild-type p53 (MKN-45), but not in mutant-type p53 (MKN-28) gastric cancer cells. The data presented suggest that downregulation of XIAP via antisense RNA can lead to apoptosis of gastric cancer cells in vitro, correlating with cellular p53 status and activation of caspase-3. This finding could lead to a potential strategy for improving the efficiency of therapies for gastric cancer.

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Acknowledgements

We thank Dr David Vaux (Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute, Australia) for his kind gift of the XIAP gene. We also appreciate Professor Dechun Li (Johns Hopkins University School of Medicine, USA), Lauren M Tarantino, and Elizabeth M Vancza (New York University School of Medicine) for their great help in the preparation of this manuscript. This study was supported by National Natural Science Foundation of China (No. 30271301, No. 30200284) and Science Foundation of Huazhong University of Science and Technology.

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Authors and Affiliations

  1. Department of Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei Province, China

    Qiang-Song Tong, Liang Wang, Fu-Qing Zeng, Fang-Min Chen & Gong-Cheng Lu

  2. Department of Pathology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei Province, China

    Li-Duan Zheng

  3. Department of Central Laboratory, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei Province, China

    Ji-Hua Dong

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  1. Qiang-Song Tong
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Correspondence to Qiang-Song Tong.

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Tong, QS., Zheng, LD., Wang, L. et al. Downregulation of XIAP expression induces apoptosis and enhances chemotherapeutic sensitivity in human gastric cancer cells. Cancer Gene Ther 12, 509–514 (2005). https://doi.org/10.1038/sj.cgt.7700813

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