In Vitro Effects of Prostaglandin E2 or Indomethacin on the Proliferation of Lymphokine-Activated Killer Cells and their Cytotoxicity against Bladder Tumor Cells in Patients with Bladder Cancer

Abstract

Purpose: To investigate the combined effects of interleukin-2 (IL-2) with either prostaglandin E₂ (PGE₂) or indomethacin (IM) on the proliferation 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 of either PGE₂ or IM by cell counting. Bladder cancer cell lines BIU-87, EJ and bladder tumor cells (BTC) from the patients were cultured as target cells, and the cytotoxicity of LAK cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, PGE₂ in samples of conditioned medium from bladder cancer cells or peripheral blood mononuclear cells (PBMC) as well as plasma from 21 patients with bladder cancer and 20 healthy donors were determined by radioimmunoassay (RIA).

Results: The proliferation of LAK cells induced by IL-2 was inhibited by PGE₂ (0.05 to 5 ng/mL) in concentration-dependent manner. The enhanced growth of LAK cells was observed at certain concentrations of IM (100–400 ng/mL) from 48 to 96 h. Pretreatment of LAK cells with IM (200 ng/mL) significantly enhanced cytotoxicity against BIU-87, EJ cells, or BTC. More PGE₂ was present in conditioned medium from BIU-87 cells than in the conditioned medium from PBMC.

Conclusions: These studies indicate that LAK cell proliferation induced by IL-2 in patients with bladder cancer is inhibited by PGE₂ produced by PBMC and bladder cancer cells. This inhibition can be overcome by IM, which may be of use in immunotherapy of bladder cancer.