engleski

Prostaglandin secretion and senstivity to indomethacin in four different murine tumours

Background and purpose. Prostaglandins (PG), especially PGE2, have tumour-promoting effect, and inhibitors of its synthesis have inhibiting effect on growth and spreading of many, but not all, tumours. We investigated the correlation of production of individual prostaglandins (PGE2, PGE1 and TxA2) and total PG production with its sensitivity to non-specific inhibitor of PG synthesis - indomethacin (INDO) in four murine tumours. Materials and Methods. CBA mice were given s.c. with either methylcholantrene-induced tumour (MCL), spontaneous carcino-sarcoma (CaSa), Ehrlich ascites carcinoma (EAC) or mastocytoma P815. Tumour growth was assessed by measuring tumour diameter. Synthesis of PGs was determined in small fragments of tumour tissue and in supernatants of tumour lines grown in vitro. The concentration of particular PGs was determined by specific RIA kits. Results. In vivo, INDO significantly inhibited the growth of MCL, while had no effect on the growth of CaSa, EAC and P815. On the other hand, long-acting prostaglandin E2 analogue, dimethyl-prostaglandin E2 (DM-PGE2), had no effect on growth of either of these tumours. In vitro, neither INDO nor DM-PGE2 had effect on the growth of MCL and CaSa. Inhibitory effect of INDO correlated with the total prostaglandin synthesis in tissue samples ex vivo ; total prostaglandin synthesis and PGE2 synthesis was significantly higher in INDO-responsive tumour MCL than in CaSa, EAC or P815. In vitro, cultured MCL cells produced about 8 times higher total amount of PGE2 than of PGI2, showing that main prostaglandin produced by tumour cells itself is PGE2. Other tumours produced in vitro significantly smaller (CaSa) or negligible amounts of PGE2 (EAC and P815). The anti-tumour effect of INDO in vivo was greatly diminished in T-cell deficient mice (TIR-mice). Conclusions. These results indicate that the anti-tumour effect of INDO correlates with either total prostaglandin production or with the PGE2 production by the tumour. The data obtained on TIR mice suggest that INDO exerts its action indirectly, via enhancement of the host's immune response.

prostaglandin secretion; indomethacin; tumours

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