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HiF-1α siRNA and Cisplatin in Combination SuppressTumor Growth in a Nude Mice Model of Esophageal Squamous Cell Carcinoma

  • Liao, Hong-Ying (Department of Thoracic Surgery, Clinical Research Center of Chest Tumor, the Third Affiliated Hospital, Sun Yat-sen University) ;
  • Wang, Gui-Ping (Department of Pharmacy, Health College, Guangzhou Medical University) ;
  • Gu, Li-Jia (Department of Thoracic Surgery, Clinical Research Center of Chest Tumor, the Third Affiliated Hospital, Sun Yat-sen University) ;
  • Huang, Shao-Hong (Department of Thoracic Surgery, Clinical Research Center of Chest Tumor, the Third Affiliated Hospital, Sun Yat-sen University) ;
  • Chen, Xiu-Ling (Department of Thoracic Surgery, Clinical Research Center of Chest Tumor, the Third Affiliated Hospital, Sun Yat-sen University) ;
  • Li, Yun (Department of Thoracic Surgery, Clinical Research Center of Chest Tumor, the Third Affiliated Hospital, Sun Yat-sen University) ;
  • Cai, Song-Wang (Department of Thoracic Surgery, Clinical Research Center of Chest Tumor, the Third Affiliated Hospital, Sun Yat-sen University)
  • Published : 2012.02.29

Abstract

Introduction: The esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances, and a current challenge is the development of effective therapeutic agents. Our present work addressed the effect of HIF-$1{\alpha}$ siRNA alone or in combination with cisplatin on the growth of ESCC in nude mice. Materials and Methods: Xenografts were established by inoculating ESCC TE-1 cells in nude mice, and transplanted tumors were treated with HIF-$1{\alpha}$ siRNA, cisplatin alone or together. Growth was assessed by measuring tumor volume. HIF-$1{\alpha}$ mRNA and protein expression were detected using RT-PCR and immunohistochemistry, respectively. Apoptosis of ESCC TE-1 cells was analyzed by flow cytometry. Results: In our nude mice model, HIF-$1{\alpha}$ siRNA effectively inhibited the growth of transplanted ESCC, downregulating HIF-$1{\alpha}$ mRNA and protein expression, and inducing ESCC TE-1 cell apoptosis. Notably when combinated with cisplatin, HIF-$1{\alpha}$ siRNA showed synergistic interaction in suppressing tumor growth. Furthermore, the proportion of apoptotic cells in HIF-$1{\alpha}$ siRNA plus cisplatin group was significantly higher than that in cisplatin or HIF-$1{\alpha}$ siRNA-treated groups (P<0.05). Conclusions: Down-regulated HIF-$1{\alpha}$ expression induced by siRNA could effectively suppress the growth of transplanted ESCC $in$ $vivo$. HIF-$1{\alpha}$ siRNA could enhance the cytotoxicity of cisplatin, which suggests that a combination of these two agents may have potential for therapy of advanced ESCC.

Keywords

RNA interference;HIF-$1{\alpha}$;cisplatin;esophageal squamous cell carcinoma

Acknowledgement

Supported by : Natural Science Foundation

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