A study of anti-angiogenic gene Endostatin for murine squamous cell carcinoma

Research Project

Project/Area Number	12671973
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Surgical dentistry
Research Institution	Kanagawa Dental College
Principal Investigator	OHMI Yasushi Kanagawa Dental College, Dentistry, assistant, 歯学部, 助手 (10318892)
Co-Investigator(Kenkyū-buntansha)	SASAKURA Yuichi Kanagawa Dental College, Dentistry, Assistant Professor, 歯学部, 講師 (80121002) LI Ushaku Kanagawa Dental College, Dentistry, assistant, 歯学部, 助手 (90288085) HIRATA Kazuya Kanagawa Dental College, Dentistry, assistant, 歯学部, 助手 (80308311)
Project Period (FY)	2000 – 2001
Project Status	Completed (Fiscal Year 2001)
Budget Amount *help	¥3,400,000 (Direct Cost: ¥3,400,000) Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000) Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywords	squamous cell carcinoma / Endostatin / 遺伝子治療
Research Abstract	To determine whether endostatin, a powerful angiogenesis inhibitor, is capabie of suppressing the tumor growth of head and neck squamous cell carcinoma in a murine model, we transfected one or the other of endostatin cDNA and Neo into mouse squamous cell carcinoma NRS-1 and SCC-VII cells in vitro. We subcutaneously implanted 2.5 x 10^6 transfected tumor cells carrying either endostatin DNA or not into 6-week-old female C3H/He mice. Tumor volumes were measured until 4 weeks. An immunohistochemical study was done using antibodies against CD31, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2). Apoptotic cells were assessed by TUNEL staining. Tumor growth was significantly inhibited when the tumor cells were transfected endostatin. Inhibition of endostatin-transfectant tumors was accompanied by a marked reduction in vascularity and by the presence of many apoptotic tumor cells. Endostatin cDNA did not affect the expression of VEGF and FGF-2 in the vascular endothelium. In this study, we have demonstrated the efficacy in suppression of endostatin gene transfer both tumor growth and tumor vascularity in a murine model, suggesting its potential efficacy in the treatment of the corresponding carcinoma in humans.