Tamoxifen increases photodynamic therapeutic response of U87 and U25ln human glioma cells

Abstract

We tested the hypothesis that Tamoxifen (TMX), an inhibitor of protein kinase C (PKC), augments the cytotoxicity of photodynamic therapy (PDT) treatment of human (U87) and (U25ln) glioma cells. U87 and U25ln glioma cells were plated and treated with PDT using Photofrin as the sensitizer. Cells were treated with Photofrin at various doses and with various optical (632 nm) irradiation intensities 24 h later. Cells were also treated with Photofrin at a fixed dose alone and with various doses of Tamoxifen and subjected to laser treatment 24 h later. Tumor response was tested using the (3-94,5-dimethyl-2-yl)-2,5-diphenyl-tetrazolium (MTT) method. Total toxicity of U87 cells was achieved with PDT at all doses of Photofrin (1, 2.5, 5, 10 microg/ml) with irradiation densities equal to or greater than 200 mJ/cm2. Using an irradiation intensity of 100 mJ/cm2, U87 and U25ln cells were killed in a Photofrin dose-dependent manner. Significant cytotoxicity was detected with Photofrin doses of 5 microg/ml (p < 0.05) and 10 microg/ml (p < 0.001). Tamoxifen at a dose of 500 microg/ml and higher, significantly increased the toxicity of the PDT response with 5 microg/ml Photofrin and 100 mJ/cm2 (p < 0.05). In summary, our data demonstrate that Tamoxifen significantly enhances the Photofrin PDT activity of U87 and U25ln human glioma cells.