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WW domain containing oxidoreductase induces apoptosis in gallbladder-derived malignant cell by upregulating expression of P73 and PUMA

  • Research Article
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Tumor Biology

Abstract

Gallbladder cancer (GBC) is one leading cause of cancer-related death worldwide. WW domain-containing oxidoreductase (WWOX) is a tumor suppressor gene which can suppress proliferation of a variety of tumors. However, little was known about the relationships between WWOX and gallbladder cancer. In the current study, we intended to investigate the tumor suppressive role of WWOX in gallbladder malignant cells both in vitro and in vivo, and explore the potential mechanism of tumor toxic function of WWOX. Our results have shown that WWOX triggerred apoptosis in GBC cells and increased the expression of P73 and PUMA in cytoplasm. We also have found that Bax has been upregulated after overexpression of WWOX, whereas, Bcl-2 was downregulated by WWOX. To further validate the results in vivo, we evaluated the tumor suppressive role of WWOX in mouse model of gallbladder cancer. The results have shown that the proliferation of the tumor was inhibited after delivery of WWOX, and the expressions of P73 and PUMA were upregulated in target tissues. The mice models administrated with WWOX have shown better prognosis than mice in negative control groups. The results from our study indicated that WWOX could be used as a therapeutic agent in the gene therapy of gallbladder cancer.

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Acknowledgments

This work is supported by grants from the Basic Research for Application Fund of Yunnan China (No. 2011FZ124 & 2012FB050) and grants from the “Doctor Innovation Fund Project of KunmingMedical University” (No. 2012D05). The work is also funded by National Natural Science Foundation of China (30660184). We give sincere thanks to Professor Huatang Zhang for his constructive suggestions to this study.

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Authors and Affiliations

  1. Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, People’s Republic of China

    Dong Wei, Xiaowen Zhang, Hao Zou, Lin Wang, Bimang Fu, Xuesong Wu, Xiao Li, Jiayun Ge, Yuehua Li, Hong Zhu, Kun Wang, Tao Wang & Pei Yang

  2. Department of Research Laboratory Center, Yan’an Affiliated Hospital of Kunming Medical University, Kunming, 650051, Yunnan, People’s Republic of China

    Zongliu Hou & Wenju Wang

  3. Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650031, Yunnan, People’s Republic of China

    Zhiling Luo

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  1. Dong Wei
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  2. Xiaowen Zhang
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  3. Hao Zou
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  4. Lin Wang
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  5. Bimang Fu
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  6. Xuesong Wu
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  8. Xiao Li
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  11. Hong Zhu
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  13. Tao Wang
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  15. Zongliu Hou
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  16. Wenju Wang
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Correspondence to Xiaowen Zhang or Wenju Wang.

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Wei, D., Zhang, X., Zou, H. et al. WW domain containing oxidoreductase induces apoptosis in gallbladder-derived malignant cell by upregulating expression of P73 and PUMA . Tumor Biol. 35, 1539–1550 (2014). https://doi.org/10.1007/s13277-013-1213-1

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  • DOI: https://doi.org/10.1007/s13277-013-1213-1

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