The interactions between indomethacin and cytotoxic drugs in mice bearing B-16 melanomas

Abstract We have compared the effects of indomethacin alone (100 μg/mouse/day) with those of indomethacin plus adriamycin, 5-FU, nitrogen mustard, thioTEPA, and vincristine on B-16 tumor cell proliferation in vivo . As we have previously descriged, after four days of treatment with indomethacin, subcutaneous tumors were slightly smaller and lighter in weight, but contained more melanoma cells. Addition of indomethacin to cytotoxic regimens resulted in either no change or a decrease in the effectiveness of the chemotherapy. In previous studies we demonstrated that treatment of tumor-bearing mice with a long-acting synthetic analogue of PGE 2 (di-M-PGE 2 ) stimulated the synthesis of endogenous prostaglandins. In order to evaluate if these endogenously synthesized prostaglandins were responsible for the inhibition of B-16 growth in vivo , mice were treated with di-M-PGE 2 or di-M-PGE 2 plus indomethacin. Addition of indomethacin did not alter the tumor inhibitory effects of di-M-PGE 2 .