Inhibition of B16 melanoma growth in vivo by retroviral vector-mediated human ribonuclease inhibitor.
Human ribonuclease inhibitor (hRI) can inhibit angiogenesis by reversibly binding angiogenin, a member of the RNaseA superfamily, and by suppressing the expression of basic fibroblast growth factor (bFGF). Angiogenesis is necessary for the growth and metastasis of tumors. To study the links between hRI, angiogenesis, and melanoma growth, the hRI gene was intravenously administered to mice in a recombinant retroviral vector, and expression of the hRI gene was induced to block melanoma angiogenesis. Expression, distribution, and contribution of the target gene in mice were assayed. The results showed that the tumors of mice in the hRI treatment group grew slower with less vascularity than those of mice in control groups. The introduced hRI gene inhibited tumor growth without causing significant side effects in the animals. More hRI expression in vimentin-positive cells of the tumor than in melanoma cells suggested that mesenchymal cells in the fibrous envelope of the tumor play important roles in this gene therapy.
Wang
Ting
T
Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116027, China.
Yang
Mingjie
M
Chen
Junxia
J
Watkins
Tonya
T
Xiuyun
Cui
C
D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000627:therapeutic use*; D000818:Animals; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D010926:Placental Hormones / Q000235:genetics / Q000627:therapeutic use*; D012190:Retroviridae / Q000235:genetics; D012260:Ribonucleases / Q000037:antagonists & inhibitors*; D014162:Transfection; D014771:Virion
D020533:Angiogenesis Inhibitors; D010926:Placental Hormones; C022052:placental ribonuclease inhibitor; D012260:Ribonucleases