Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Tas13D Inhibits Growth of SMMC-7721 Cell via Suppression VEGF and EGF Expression

  • He, Huai-Zhen (School of Medicine, Xi'an Jiaotong University) ;
  • Wang, Nan (School of Medicine, Xi'an Jiaotong University) ;
  • Zhang, Jie (School of Medicine, Xi'an Jiaotong University) ;
  • Zheng, Lei (School of Medicine, Xi'an Jiaotong University) ;
  • Zhang, Yan-Min (School of Medicine, Xi'an Jiaotong University)
  • Published : 2012.05.30
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Abstract

Objective: Taspine, isolated from Radix et Rhizoma Leonticis has demosntrated potential proctiective effects against cancer. Tas13D, a novel taspine derivative synthetized by structure-based drug design, have been shown to possess interesting biological and pharmacological activities. The current study was designed to evaluate its antiproliferative activity and underlying mechanisms. Methods: Antiproliferative activity of tas13D was evaluated by xenograft in athymic mice in vivo, and by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and cell migration assays with human liver cancer (SMMC-7721) cell lines in vitro. Docking between tas13D and VEGFR and EGFR was studied by with a Sybyl/Surflex module. VEGF and EGF and their receptor expression was determined by ELISA and real-time PCR methods, respectively. Results: Our present study showed that tas13D inhibited SMMC-7721 xenograft tumor growth, bound tightly with the active site of kinase domains of EGFR and VEGFR, and reduced SMMC-7721 cell proliferation (IC=34.7 ${\mu}mol/L$) and migration compared to negative controls. VEGF and EGF mRNAs were significantly reduced by tas13D treatment in a dose-dependent manner, along with VEGF and EGF production. Conclusion: The obtained results suggest that tas13D inhibits tumor growth and cell proliferation by inhibiting cell migration, downregulating mRNA expression of VEGF and EGF, and decreasing angiogenic factor production. Tas13D deserves further consideration as a chemotherapeutic agent.

Keywords

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