The application of an anti-angiogenic gene (thrombospondin-1) in the treatment of human prostate cancer xenografts.
Angiogenesis is a critical event for solid tumor growth and metastasis. Within a given microenvironment, the angiogenic response is determined in part by the balance between angiogenesis inducers and inhibitors. The aim of this study was to establish a thrombospondin-1 (TSP-1) ( an antiangiogenic gene) expression vector, and to determine the feasibility for use of TSP-1 in prostate cancer gene therapy. The results of this study showed that pCR-TSP-1, the cloned TSP-1 expression plasmid vector, expressed the TSP-1 gene efficiently in DU145, a human prostate cancer cell line. pCR -TSP-1 did not exert any significant growth inhibitory activity on the tested cell line in vitro. However, TSP-1 overexpression inhibited the growth of DU-145 xenografts in Balb/c nude mice when directly transfected with pCR-TSP-1 in combination with a liposomal agent (DOSPER). Histological analysis showed that there were extensive areas of necrosis in the TSP-1 overexpressing tumors, whereas no necrotic foci were observed in the control tumors. Furthermore, the microvessel density was lower in the TSP-1 overexpressing tumors compared to the control tumors. These results suggest that TSP-1 may be a potentially useful gene for prostate cancer gene therapy.
Jin
R J
RJ
Deparment of Urology, Seoul National Untiversity College of Medicine, South Korea.
Kwak
C
C
Lee
S G
SG
Lee
C H
CH
Soo
C G
CG
Park
M S
MS
Lee
E
E
Lee
S E
SE
D000818:Animals; D015153:Blotting, Western; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007124:Immunoenzyme Techniques; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019700:Thrombospondin 1 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
D008081:Liposomes; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019700:Thrombospondin 1