Gene therapy of human bladder cancer with adenovirus-mediated antisense basic fibroblast growth factor

K. Inoue, P. Perrotte, Christopher G Wood, J. W. Slaton, P. Sweeney, Colin P Dinney

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Abstract

We previously investigated the role of basic fibroblast growth factor (bFGF) as a mediator of angiogenesis, tumorigenicity, and metastasis of transitional cell carcinoma (TCC) of the bladder. In the present study, we determined whether adenoviral-mediated antisense bFGF gene transfer therapy (Ad bFGF-AS) would inhibit TCCs growing in the subcutis of nude mice. In vitro, Ad bFGF-AS inhibited endothelial cell proliferation and enhanced apoptosis. The highly metastatic human TCC cell line 253J-BV(R) was implanted ectopically in the subcutis of athymic nude mice, and therapy was begun when the tumors reached a diameter between 5 and 7 mm. Intralesional therapy with Ad bFGF-AS decreased the in vivo expression of bFGF and matrix metalloproteinase type 9 mRNA and protein, and reduced microvessel density and enhanced endothelial cell apoptosis. Tumor growth was significantly inhibited by Ad bFGF-AS (mean, 58 mg) compared with controls [saline (mean, 562 mg), β-galactosidase adenovirus (mean, 586 mg), and sense bFGF adenoviral therapy (Ad bFGF-S; mean, 3012 mg)]. These results suggest that Ad bFGF-AS therapy affects endothelial cells directly and tumor cells indirectly through down-regulation of bFGF and matrix metalloproteinase type 9, resulting in endothelial cell apoptosis and significant tumor growth inhibition. Furthermore, these studies confirm that bFGF expression is a valid target for the therapy of bladder cancer.

Original languageEnglish (US)
Pages (from-to)4422-4431
Number of pages10
JournalClinical Cancer Research
Volume6
Issue number11
StatePublished - Nov 27 2000

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Fibroblast Growth Factor 2
Urinary Bladder Neoplasms
Adenoviridae
Genetic Therapy
Endothelial Cells
Nude Mice
Transitional Cell Carcinoma
Matrix Metalloproteinase 9
Apoptosis
Neoplasms
Galactosidases
Therapeutics
Growth
Microvessels
Urinary Bladder
Down-Regulation
Cell Proliferation
Neoplasm Metastasis
Cell Line

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Gene therapy of human bladder cancer with adenovirus-mediated antisense basic fibroblast growth factor. / Inoue, K.; Perrotte, P.; Wood, Christopher G; Slaton, J. W.; Sweeney, P.; Dinney, Colin P.

In: Clinical Cancer Research, Vol. 6, No. 11, 27.11.2000, p. 4422-4431.

Research output: Contribution to journalArticle

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