Synergism between cisplatin and radiotherapy in an in vitro prostate tumor cell line

Background: A combination of local irradiation and systemic cytotoxic treatment could improve therapeutic efficacy in metastatic prostate cancer. Radiosensitization can augment the treatment response to standard doses of radiation or enable lower treatment doses to be given; thus decreasing possible side effect. Intracellular glutathione has been implicated in the mechanism of such radio- sensitizing effects. Materials and Methods: In the present study, R3327-MATLyLu prostate tumor cells were treated with cisplatin (0.0325 μM, 0.1625 μM, 0.325 μM and control '0 μM') in combination with irradiation (2, 4, 6, 8 Gy and control '0 Gy'). The survival of clonogenic tumor cells in agar was determined. In another experiment the irradiation was carried out after a 3 hours pretreatment with cisplatin concentrations (1.63 μM, 3.25 μM, 6.5 μM and control '0 μM') both in the presence and absence of Glutathione. Results: In both experimental conditions the combination of cisplatin with irradiation yielded significant supra-additive treatment effects. Conclusions: The analysis of combination treatment effects, using two different methods confirmed the existence of synergism. The presence of a high level of extracellular glutathione did not alter the radiosensitization effects observed without glutathione, suggesting that the presence of glutathione may not be a major limiting factor in the radiosensitization effects observed in the investigations.