Interaction between low dose-rate irradiation, mild hyperthermia and low-dose caffeine in a human lung cancer cell line.

Purpose: To investigate cell killing by means of low dose-rate irradiation (LDRI) combined with concurrent mild hyperthermia and to determine the effect of low-dose caffeine on this combination treatment. Materials and methods: Human lung adenocarcinoma cells, LK87, were treated with LDRI (50cGy/h) in combination with mild hyperthermia at 41 C and low-dose caffeine (1mm). Cell survival was estimated by clonogenic assay. Flow-cytometry was performed with PI staining using FACScan. Heat-shock protein (HSP72/73) was measured by the Western blotting method. All treatments were simultaneously performed for up to 48h (24Gy). Results: LDRI cytotoxicities were enhanced by hyperthermia at 41 C. D0 calculated from the dose-response curve for LDRI combined with 41 C was 3.46Gy whereas it was 6.55Gy for LDRI alone. The survival curve for LDRI+41 C demonstrated no chronic thermotolerance up to 48h. For LDRI+simultaneous low-dose caffeine, cell killing was also enhanced, where D0 was 3.38Gy at 37 C. Radiosensitization caused by caffeine was enhanced by combination with simultaneous mild hyperthermia at 41 C, where D0=1.78Gy. Cell cycle analysis demonstrated remarkable G2 and mild G1 arrest for LDRI alone, but only G arrest was observed for L1DRI combined with 41 C and for LDRI combined with caffeine. Strong and early G1 arrest was observed in the treatment with LDRI+caffeine at 41 C. The amount of HSP72/73 in the combination of LDRI with caffeine at 41 C was less than that at 41 C alone. Conclusion: LDRI cytotoxicity was enhanced by non-lethal hyperthermia. Low dose caffeine produced further cell killing in the combination of LDRI with mild hyperthermia. [ABSTRACT FROM AUTHOR]