A Small Interfering RNA Targeting Vascular Endothelial Growth Factor Inhibits Ewing's Sarcoma Growth in a Xenograft Mouse Model

• Hui Guan

  1Division of Pediatrics and Departments of

• Zhichao Zhou

  1Division of Pediatrics and Departments of

• Hua Wang

  2Cancer Biology and

• Shu-Fang Jia

  1Division of Pediatrics and Departments of

• Wenbiao Liu

  3Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas

• Eugenie S. Kleinerman

  1Division of Pediatrics and Departments of

抄録

Angiogenesis plays an essential role in tumor growth and metastasis and is a promising therapeutic target for cancer. Vascular endothelial growth factor (VEGF) is a key regulator in vasculogenesis as well as in angiogenesis. TC71 human Ewing's sarcoma cells overexpress VEGF, with a shift in isoform production from membrane-bound VEGF189 to the more soluble VEGF165. Transfection of TC71 cells with a vector-based VEGF targeted small interfering RNA expression system (VEGFsi) inhibited VEGF165 expression by 80% and VEGF165 protein production by 98%, with no alteration in VEGF189 expression. Human microvascular endothelial cell proliferation and migration induced by conditioned medium from VEGFsi-transfected TC71 cells was significantly less than that induced by conditioned medium from TC71 cells and control vector-transfected TC71 cells. Furthermore, after s.c. injection into athymic nu/nu mice, the tumor growth of VEGFsi-expressing TC71 cells was significantly less than that of parental or control vector-transfected cells. Vessel density as assessed by CD31 immunohistochemical analysis and VEGF165 expression as assessed by Northern blotting were also decreased. Intratumor gene therapy with polyethylenimine/VEGFsi also resulted in tumor growth suppression. When inoculated into the tibias of nude mice, VEGFsi-expressing TC71 cells induced osteolytic bone lesions that were less severe than those induced by control groups. These data suggest that targeting VEGF165 may provide a therapeutic option for Ewing's sarcoma.

収録刊行物

• Clinical Cancer Research

  Clinical Cancer Research 11 (7), 2662-2669, 2005-04-01

  American Association for Cancer Research (AACR)

キーワード

• Cancer Research
• Oncology

詳細情報

• CRID: 1362825895703095040
• NII論文ID: 30018691005
• DOI: 10.1158/1078-0432.ccr-04-1206
• ISSN: 15573265
• ISSN: 10780432
• Web Site: https://aacrjournals.org/clincancerres/article-pdf/11/7/2662/1963015/2662-2669.pdf
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