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.

Indomethacin Influences Moloney's Sarcoma and Associated Periosteal Osteogenesis in the Mouse

“…Our results indirectly confirm data of Strausser and Humes (1975), who reported an increase in prostaglandin E in MSV-induced tumors. The level of prostaglandin has been shown to increase with tumor diameter and to decrease with tumor regression.…”

Studies of Cell Subpopulations Mediating Mitogen Hyporesponsiveness in Patients with Hodgkin's Disease

“…It is possible that the secretion of an active substance by the suppressor cells causes an increased intracellular cyclic AMP. Prostaglandins can cause such an increase, and it is possible they might be involved (40)(41)(42). Preliminary in vitro evidence from a limited number of patients with HD in our laboratory has demonstrated a dramatic increase in PHA responsiveness of HD lymphocytes upon administration of indomethacin, a prostaglandin synthetase inhibitor.…”

Failure of short-term treatment with flurbiprofen to enhance the therapeutic effect of cyclophosphamide against rodent sarcomas and a leukaemia

“…Experiments in which anti-inflammatory drugs (NSAID) alone have been administered to tumour-bearing animals have yielded disparate results: some authors have recorded that such treatment did not affect tumour growth (Sykes & Maddox, 1972;Powles et al, 1978) whilst others have found it inhibited (Tashjian et al, 1973;Plescia et al, 1975;Hial et al, 1976) and animal survival increased (Strausser & Humes, 1975;Lynch et al, 1978) particularly if treatment with the NSAID was initiated at the same time as tumour inoculation Trevisani et al, 1980). As FP was administered for only a short period during tumour growth in this study, further experiments were performed in which FP treatment was initiated the day of tumour inoculation and continued daily until resection; this protocol also failed to affect the growth and dissemination of the sarcomas, as reported elsewhere (Heckford, 1980).…”