Prostaglandin synthesis inhibition: effect on bone changes and sarcoma tumor induction in balb/c mice

Abstract

An increase in prostaglandins (PGs) of the E series has been demonstrated in Moloney sarcoma virus (MSV)-induced leg tumors of 6-week-old BALB/c male mice. The level of the hormone has been shown to increase with the tumor diameter and decrease with tumor regression. At the peak of tumor size the tibial bones of the mice were considerably deformed, suggesting osteoclastic activity. The systemic calcium level was not elevated, indicating possible release of calcium into the local tumorous area. In mice treated with indomethacin the tumors failed to develop and PG levels were markedly lower. Tibial bones of treated mice were similar in appearance to those of control, non-tumorous mice. PG levels of DBA/1J mice bearing extensive Cloudaman S91 melanomas were not elevated and no bone deformation was seen. When contrasted with studies of immuno-depressed mice the results suggest that indomethacin acted in conjunction with and possibly to restore the PG-induced depression of the immune system in preventing tumor development. It is also hypothesized that indomethacin, by suppressing the PG-mediated calcium release from bone, could be operative in inhibiting tumor growth.