Interferons have antiproliferative activity against various tumor cells in vitro, and induce differentiation or modulate surface antigen expression of cells. However in vivo antitumor effects of interferons are not always predictable because of
environmental differences and possible indirect effects via host immune system. This study was aimed to evaluate in vivo effects of recombinant human IFN-α and γ using nude mouse xenografts of human tumor. Malignant melanoma cell line A375 was
adapted
to grow as subcutaneous xenografts in athymic nude mice, which were then treated with daily s.c. injections of human IFN αor γ in dosages of 1×10E5U or 5×10E5U/mouse/day. IFNα was given at 2 timings; from the next day of tumor
transplantation
or
after tumor development. Tumors were measured twice a week, and mice were observed with time. Both IFN-αandγ showed significant antitumor effects with dose-dependency in early administration of IFN-α. And without difference between α and γ.
Histologic examination of excised tumors revealed degeneration, nuclear pyknosis, and death of cells. Rate of necrosis per unit area, calculated after measurement using image analyzer, was significantly high with IFN-γ 1×10E5U treatment.
Proliferative
activity of the tumor, estimated by mitotic frequency and proliferating cell nuclear antigen-positivity on immunohistochemical stain, was not significantly altered by IFN-α or γ. Expression of major histocompatibility complex antigen and
epidermal
growth factor receptor, visualized by immunohistochemical stain, was not modulated by in vivo IFN treatment. Spleen natural killer activity of mice was not affected by human interferons. These data showed that recombinant human IFN-α and γ had
direct
in vivo antitumor effects on A375 cells; IFN-γ might exert its antitumor effects via cytotoxic than cytostatic mechanisms; and in vivo modulation of surface antigen expression by interferons was not confirmed in A375 cell line.
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