Endostatin gene therapy on murine lung metastases model utilizing cationic vector-mediated intravenous gene delivery.
Tumors require ongoing angiogenesis to support their growth. Inhibition of angiogenesis by production of antiangiogenic factors should be a viable approach for cancer gene therapy. In this study, we investigated whether intravenous administration of endostatin gene complexed with a cationic vector (GL67/DOPE or PEI22K) could inhibit the development of lung tumors in mice injected i.v. with NFSa Y83 fibrosarcoma cells (5 x 10(5)) which frequently form lung metastasis. mRNA and protein of the transfected gene were produced in the lung and other organs of the transfected mice as assessed by immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction. Single intravenous injection of the endostatin gene (60 microg) complexed with either GL67/DOPE or PEI22K on day 3 or day 7 after fibrosarcoma cell inoculation significantly inhibited tumor formation in the lung as evidenced by the reduced number of lung tumors and lung weight, and prolonged survival of the endostatin gene-transfected mice compared with control mice. These findings suggested that the endostatin gene therapy, using cationic vector-mediated intravenous gene transfer, might be a feasible strategy for organ-targeted prevention and regulation of possible disseminated cancers.
Nakashima
Y
Y
Department of Surgery II, Nagoya City University Medical School, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Yano
M
M
Kobayashi
Y
Y
Moriyama
S
S
Sasaki
H
H
Toyama
T
T
Yamashita
H
H
Fukai
I
I
Iwase
H
H
Yamakawa
Y
Y
Fujii
Y
Y
D000818:Animals; D019556:COS Cells; D003094:Collagen / Q000032:analysis / Q000235:genetics*; D043169:Endostatins; D005354:Fibrosarcoma / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D007150:Immunohistochemistry / Q000379:methods; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D023421:Models, Animal; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured
D043169:Endostatins; D010446:Peptide Fragments; D012333:RNA, Messenger; D003094:Collagen