Combining proton or photon irradiation with epothilone B : An in vitro study of cytotoxicity in human cancer cells

Recently, the use of proton beams in cancer therapy is becoming widespread, and tumour treatment modalities combining radiosensitizing chemical agents with irradiation are under investigation in order to achieve greater tumour local control and reduce the probability of distant failures. The combined treatment modality of radiation and the clinically relevant microtubule-stabilizing compound epothilone B is a promising approach for anticancer therapy. In the present study, we investigated the cytotoxicity of a spread out Bragg peak (SOBP) proton beam, as well as of 6 MV photons, in human glioblastoma (U251 MG) and lung adenocarcinoma (A549) cells pretreated for 24 h, or not, with epothilone B at concentrations of 0.125 and 0.075 nM respectively. Proton irradiation was performed at the middle position of an actively modulated SOBP (12–18 cm depth in water) and cell survival was evaluated by a colony forming assay. For both cell lines, survival curves after proton or photon irradiation alone showed linear quadratic behaviour with proton RBE (relative biological effectiveness), compared with photons at 10% survival, of 1.5 ± 0.2. Treatment of cells with epothilone B at subnanomolar concentration has an anticlonogenic effect. Furthermore, differently from the results found with radiation alone, the survival curves for the combined treatment epothilone B–radiation showed a linear trend and analysis of the interaction of the two cytotoxic agents indicated a slight synergism. These data provide a radiobiological basis for further experiments, as well as clinical studies.