Enhancement of prostate cancer xenograft growth with whole-body radiation and vascular endothelial growth factor.
Prostate cancer research has been limited by the slow growth of human prostate tumors In athymic rodent models. This study sought to determine if low-dose radiation and vascular endothelial growth factor (VEGF) could enhance the development of PC-3 human prostate adenocarcinoma xenotransplanted into nude mice. Whole body radiation (2 Gy) was delivered only once, whereas VEGF (39 ng total/mouse) was injected subcutaneously over a 17-day period. The combination of the two agents, compared to nontreated controls, resulted in significantly higher tumor incidence (100% versus 50%) and more-rapid tumor progression (1288 mm3 versus 190 mm3 by day 60). Treatment-associated changes were observed in body weights and assays of blood and spleen cells. In addition, 3H-thymidine uptake by PC-3 cells cultured in the presence of VEGF and transforming growth factor-beta 1 was compared. These results show that low-dose, whole-body radiation and VEGF can be used in concert safely and effectively to facilitate growth of PC-3 prostate tumor and that the mechanisms of interaction may involve leukocyte modulation.
Gridley
D S
DS
Loma Linda University/Independent Order of Foresters Cancer Research Laboratory, Department of Microbiology and Molecular Genetics, CA 92350, USA. dgridley@ccmail.llu.edu
Andres
M L
ML
Slater
J M
JM
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000633:toxicity*; D006801:Humans; D008222:Lymphokines / Q000633:toxicity*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D011471:Prostatic Neoplasms / Q000473:pathology*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014916:Whole-Body Irradiation
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors