The application of an antiangiogenic gene (thrombospondin-1) in the treatment of human prostate cancer xenografts

Abstract

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. Cancer Gene Therapy (2000) 7, 1537–1542.