The purpose of these studies was to determine whether systemic administration of IFN-α can inhibit the expression of basic fibroblast growth factor (bFGF) in human transitional cell carcinoma, reduce its angiogenesis, and thus inhibit its growth in the bladder wall of nude mice. In vitro incubation of the highly metastatic 253J B-V cells and the IFN-α-resistant 253J B-V IFNR cells with noncytostatic concentrations of IFN-α downregulated the steady-state mRNA transcripts and protein production of bFGF. IFN-α-insensitive and IFN-α-resistant cells were implanted in the bladder wall of nude mice. Systemic administration of IFN-α decreased the in vivo expression of bFGF, decreased blood vessel density in the tumors, and inhibited tumor growth of both IFN-α-insensitive and IFN-α-resistant cells. These data suggest that in addition to its well-documented antiproliferative effects, IFN-α can inhibit the growth of human bladder cancer cells by inhibition of angiogenesis.

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Supported in part by NIH Grant R29 CA67914-01 (to C. P. N. D.), the American Foundation for Urologic Disease (to C. P. N. D.), M. D. Anderson Cancer Center Support Core Grant CA 16672, and Grant R35-CA42107 (to I. J. F.) from the National Cancer Institute, NIH, and the University Cancer Foundation.

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