IN-VITRO EFFECTS OF PROSTAGLANDIN E-2 OR INDOMETHACIN ON THE PROLIFERATION OF LYMPHOKINE-ACTIVATED KILLER-CELLS AND THEIR CYTOTOXICITY AGAINST BLADDER-TUMOR CELLS IN PATIENTS WITH BLADDER-CANCER

Purpose: To investigate the combined effects of interleukin-2 (IL-2) w ith either prostaglandin E-2 (PGE(2)) or indomethacin (IM) on the prol iferation and cytolysis of bladder tumor cells by lymphokine-activated killer (LAK) cells in patients with bladder cancer. Methods: LAK cell proliferation was assayed in the presence of various concentrations o f either PGE(2) or IM by cell counting. Bladder cancer cell lines BIU- 87, EJ and bladder tumor cells (ETC) from the patients were cultured a s target cells, and the cytotoxicity of LAK cells was determined by (4 ,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, PGE(2) in samples of conditioned medium from bladder canc er cells or peripheral blood mononuclear cells (PBMC) as well as plasm a from 21 patients with bladder cancer and 20 healthy donors were dete rmined by radioimmunoassay (RIA). Results: The proliferation of LAK ce lls induced by IL-2 was inhibited by PGE(2) (0.05 to 5 ng/mL) in conce ntuation-dependent manner. The enhanced growth of LAK cells was observ ed at certain concentrations of IM (100-400 ng/mL) from 48 to 96 h. Pr etreatment of LAK cells with IM (200 ng/mL) significantly enhanced cyt otoxicity against BIU-87, EJ cells, or BTC. More PGE(2) was present in conditioned medium from BIU-87 cells than in the conditioned medium f rom PBMC. Conclusions: These studies indicate that LAK cell proliferat ion induced by IL-2 in patients with bladder cancer is inhibited by PG E(2) produced by PBMC and bladder cancer cells. This inhibition can be overcome by IM, which may be of use in immunotherapy of bladder cance r.