Treatment of mouse carcinoma in vivo with a prostaglandin E2 analogue and indomethacin

Abstract

WHT/Ht mice transplanted s.c. with NC carcinoma were treated with 16,16-dimethyl prostaglandin E2 methyl ester (di-me-PGE2) and/or indomethacin. Each primary tumour was excised under anaesthesia 3 weeks after transplantation, weighed and extracted for prostaglandins. Mouse survival time and tumour recurrence were measured. Di-me-PGE2 10 micrograms, injected at the tumour site on alternate days from day 1 to 19, indomethacin 2.5 mg kg-1 daily by mouth, or both drugs together resulted in lighter tumours (respectively 45, 45 and 52% less, n = 18 to 20 per group, P less than 0.02) compared with vehicle-treated controls. Indomethacin reduced the tumour prostaglandin yield, but the biological activity in extracts of tumours from mice given di-me-PGE2 was high. The median survival time was longer in mice receiving indomethacin alone (61 days from tumour transplantation compared with 50 days in controls P less than 0.02). Di-me-PGE2 alone had little or no effect on survival (median 48 days) but counteracted the increase with indomethacin (di-me-PGE2 + indomethacin, 49 days median survival). There were no obvious effects of the treatments on tumour recurrence at the excision site, but there was a higher incidence of involved lymph nodes in mice given di-me-PGE2.