In vivo effects of indomethacin on the growth of murine mammary tumors

Abstract

We have examined the effect of the prostaglandin synthesis inhibitor indomethacin on the s.c. growth of three murine mammary tumors that are heterogeneous with regard to immunogenicity, metastatic ability, in situ prostaglandin levels, and many other characteristics. Continuous p.o. administration of indomethacin, beginning on the day of tumor transplantation, led to complete regression of the poorly metastatic, low-prostaglandin E (PGE), highly immunogenic Tumor 410 in 11 of 12 animals, whereas 83% of ethyl alcohol-treated controls developed progressively growing tumors. The high-PGE, highly metastatic, poorly immunogenic Tumor 4501 was partially inhibited by p.o. indomethacin, resulting in an increased survival time for tumor-bearing mice (89 days versus 53 days for controls). Progressive growth of the high-PGE, highly metastatic, poorly immunogenic Tumor 4526 was seen in 26% of indomethacin-treated mice compared to progressive growth in 80% of control mice. In contrast, when these tumor cells were cultured in vitro in the presence of indomethacin, slight stimulation of cell division was seen, suggesting that indomethacin-mediated growth inhibition in vivo is not due to direct inhibitory effects of indomethacin on tumor cells.