Potentiated antitumor effects of interleukin 12 and matrix metalloproteinase inhibitor batimastat against B16F10 melanoma in mice
Dabrowska, A.; Giermasz, A.; Marczak, M.; Gołab, J.; Jakóbisiak, M.
Anticancer Research 20(1a): 391-394
2000
ISSN/ISBN: 0250-7005 PMID: 10769685 Document Number: 515654
The application of antiangiogenic agents in cancer therapy has been studied extensively. Combination of agents with antiangiogenic properties could possibly enhance antitumor effects. Interleukin 12 is a cytokine with potent antitumor activity mediated also via antiangiogenic mechanisms. These effects are attributed to IFN-gamma production stimulated by IL-12. Since IFN-gamma has been reported to augment antitumor effects when combined with one of the metalloproteinase inhibitors - batimastat (BB-94), we have examined a combined treatment with IL-12 and BB-94 in a murine melanoma model. The administration of both agents showed potentiated antitumor activity. Furthermore, we have shown in a tumor-induced angiogenesis model that the combined application of IL-12 and batimastat inhibits the formation of new blood vessels to a greater extent than either agent alone. Our observations show that antiangiogenic effects are at least partly responsible for the enhanced antitumor effects of the combined treatment with IL-12 and BB-94.