Effects of arachidonic acid metabolites in a murine model of squamous cellcarcinoma

Background. A murine model (C3H mice) of squamous cell carcinoma (SCCVII) h as been used to investigate the role of arachidonic acid (AA) metabolites i n head and neck cancer. Inhibition of tumor growth by cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors of AA metabolism has been associated with changes in levels of AA metabolites in tumor tissues and inflammatory cell infiltrates. To characterize this model further, the effects of exogenous AA metabolites on tumor growth in vitro and in vivo were investigated. Methods. Following subcutaneous inoculation with SCCVII tumor cells, contro l (16 mice) and treatment (24 mice) groups were injected with peritumoral v ehicle or AA metabolite. Peritumoral injections of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and 12-hydroxyeicosatetraenoic acid (12-HETE) were performed for 16-21 days, and final excised tumor weights were measured. In vitro production of PGE2 and LTB4 was assayed in 2-5 day cultures of SCCVI I. Exogenous PGE2 effects on tumor cell growth was assessed with the MTT as say in vitro. Results. Tumor growth was significantly inhibited (p = .03) following perit umoral injection of PGE2. Final tumor weights were not affected by LTB4 or 12-HETE. Tumor inhibition by PGE2 was associated with increased tumor tissu e levels of LTB4 (p = .04). In vitro, SCCVII produced minimal amounts of PG E2 and LTB4, and PGE2 had minimal effect on growth. Conclusions. In this model, tumor inhibition by exogenous PGE2 is primarily mediated by affecting host-tumor interactions, although there may be some direct effect on tumor cells. Changes in tumor tissue levels of LTB4 follow ing peritumoral PGE2 administration may be attributable to negative feedbac k inhibition of the COX pathway with shunting into the LOX pathway. SCCVII cells are probably not a significant source of prostaglandins and leukotrie nes in vivo. These data provide insight into the mechanism of action of inh ibitors of AA metabolism on tumor growth. (C) 2000 John Wiley & Sons, Inc.