Inhibition of tumor growth through suppression of angiogenesis by brain-specific angiogenesis inhibitor 1 gene transfer in murine renal cell carcinoma.
This study was designed to elucidate the therapeutic effect of transfering the brain-specific angiogenesis inhibitor 1 (BAI1) gene to a mouse renal cell carcinoma cell line (Renca). Female BALB/c mice were inoculated subcutaneously with wild-type Renca (Renca/Wild) cells or Renca cells transfected with the BAI-1 (Renca/BAI-1) or LacZ (Renca/LacZ) gene. Tumor growth was observed every other day from 3 to 35 days after implantation. Moreover, the intratumoral injection of the adenovirus vector containing the gene encoding BAI1 was conducted at two-day intervals from 11 to 31 days after implantation of the Renca/Wild or Renca/BAI1 tumor. Tumor blood flow was measured by colorimetric angiogenesis assay (CAA). The concentration of the vascular endothelial growth factor (VEGF) in the cell culture supernatants was determined by enzyme-linked immunoassay. The size of the Renca/BAI1 tumor was significantly (p<0.01) suppressed compared to the Renca/Wild and Renca/LacZ tumors 21 days after tumor implantation. The injection of the BAI1 viral vector at 2-day intervals significantly inhibited the growth of both the Renca/Wild and Renca/BAI1 tumors. The blood volume measured by CAA and microvessel density was significantly lower in the Renca/BAI1 than in the Renca/Wild and Renca/LacZ tumors (p<0.01 and p<0.05, respectively). A significant (p<0.01) reduction in VEGF concentration in the supernatant was demonstrated in the Renca/BAI1 compared with the Renca/Wild and Renca/LacZ cell cultures. These observations suggest that the transfer of the BAI1 gene to Renca can suppress the tumor growth via the inhibition of angiogenesis. The down-regulation of VEGF production in tumor cells contributes to this anti-tumor effect.
Kudo
Shigetaka
S
Department of Urology, Iwate Medical University School of Medicine, Morioka 020-8505, Japan.
Konda
Ryuichiro
R
Obara
Wataru
W
Kudo
Daisuke
D
Tani
Kenzaburo
K
Nakamura
Yusuke
Y
Fujioka
Tomoaki
T
D042501:Angiogenic Proteins / Q000235:genetics*; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D018076:DNA, Complementary / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D043562:Receptors, G-Protein-Coupled; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays