Endostatin gene transfection using a cationic lipid: advantages of transfection before tumor cell inoculation and repeated transfection.
Intravenous endostatin gene transfection results in tumor suppression in a murine pulmonary metastasis model. We transfected the endostatin gene at different times, in order to achieve an optimal protective effect. pST2-Endo encoding murine endostatin was injected in a complex with cationic lipid. Pulmonary metastases were caused by intravenous injection of murine fibrosarcoma cells. Mice were observed for 14 days following fibrosarcoma cell inoculation (FSI). In the study groups, the animals were transfected with pST2-Endo at three different times: 2 days before and 3 and 7 days after FSI. In the group transfected with pST2-Endo 2 days before FSI, the weights of the lungs and tumor-occupied area ratio were significantly less than in the other groups. Significant inhibition of tumor neovascularization was documented by means of CD31 immunohistochemistry. The effect of repeated endostatin transfection on survival after FSI was determined. Animals repeatedly transfected with the endostatin gene survived significantly longer than the groups treated with a single endostatin gene transfection. A stable endostatin-expressing fibrosarcoma transfectant was created and tested for migration and invasion. Compared with controls, endostatin expression reduced migration and invasion by 15%. It is concluded that endostation gene transfection before FSI and repeated transfection thereafter results in significant tumor suppression.
Yano
Motoki
M
Department of Surgery II, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan. motoki@med.nagoya-cu.ac.jp
Nakashima
Yoshiaki
Y
Kobayashi
Yoshihiro
Y
Mizuno
Kotaro
K
Konishi
Akimitsu
A
Sasaki
Hidefumi
H
Fukai
Ichiro
I
Scheule
Ronald K
RK
Fujii
Yoshitaka
Y
D000818:Animals; D002470:Cell Survival / Q000235:genetics; D043169:Endostatins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D005354:Fibrosarcoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D015316:Genetic Therapy; D005822:Genetic Vectors; D008055:Lipids; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009389:Neovascularization, Pathologic / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology; D014162:Transfection / Q000379:methods
D043169:Endostatins; D008055:Lipids; D019408:Platelet Endothelial Cell Adhesion Molecule-1