Downregulation of stathmin is involved in malignant phenotype reversion and cell apoptosis in esophageal squamous cell carcinoma

Authors

  • Feng Wang MD,

    1. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
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  • Liu-Xing Wang MD,

    1. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
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  • Sheng-Lei Li MD,

    1. Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Tumor Pathology, Zhengzhou, Henan, P.R. China
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  • Ke Li MD,

    1. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
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  • Wei He MD,

    1. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
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  • Hong-Tao Liu MD,

    Corresponding author
    1. Laboratory for Cell Biology, Department of Bioengineering of Zhengzhou University, Zhengzhou, Henan, P.R. China
    • Laboratory for Cell Biology, Department of Bioengineering of Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
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  • Qing-Xia Fan MD

    Corresponding author
    1. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
    • Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China. Fax: 86-371-66295953.
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Abstract

Background and Objectives

Stathmin plays a critical role in the regulation of mitosis and mediates the development of malignant tumors. Here, we investigated the potential role of stathmin in cell cycle and apoptosis in esophageal squamous cell carcinoma (ESCC).

Methods

A stathmin short hairpin RNA (shRNA) plasmid was employed to downregulate stathmin expression in the ESCC cell line EC9706 cells. Cell proliferation was measured by cell counting, MTT, and colony formation assay. Cell migration was measured by Boyden chamber. Western blot was used to analyze the expressions of stathmin, survivin, and apoptosis-related proteins in transfected cells. Cell cycle and apoptosis were determined by flow cytometry and DNA ladder. Oncogenicity assay in nude mice was utilized to analyze phenotypic changes of transfected cells in vivo.

Results

After transfection with stathmin shRNA plasmid, stathmin expression markedly decreased in EC9706 cells. Stathmin downregulation significantly inhibited cell proliferation, cell migration in vitro, and tumorigenicity in vivo, meanwhile arrested cell cycle in the G2/M phase and induced cell apoptosis. Further, stathmin downregulation resulted in downregulation of Bcl-2 and survivin proteins, activation of Caspase-3.

Conclusions

These findings demonstrate that stathmin may play an essential role in carcinogenesis of ESCC, which will lay a foundation for target therapy of ESCC. J. Surg. Oncol. 2011;103:704–715. © 2011 Wiley-Liss, Inc.

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