Mechanism of enhancement effect of carbon-beam irradiation and topoisomerase II inhibitor on two cell lines with different radiosensitivities and different p53 status in vitro

摘要

Purpose: We investigate the differences between two tumor cell lines with different radiosensitivities in sensitivity to high-LET heavy ion beam and in sensitizing effect, and the mechanism of cisplatin and etoposide in combination with heavy-ion beam. Materials and Methods: NMT-1 (wild-type p53 cell) is a parent radiosensitive cell line and NMT-1R (mutant-type p53 cell) is a variant radioresistant cell line. Heavy-ion (carbon ion) was accelerated by a heavy-ion medical accerelator in Chiba at National Institute of Radiological Sciences. The RBE of the carbon ion beams to X-rays was calculated for D10 (10% survival dose). The mechanism of the enhancement effect was investigated by apoptosis, cell cycle, and DNA repair function (expression of Ku70 protein). Results: There was no significant difference between both cells in sensitivity to carbon beam irradiation and no shoulder in dose-response curve. The RBE of carbon-beam was larger in mutant-type p53 cells than in wild-type p53 cells. Etoposide showed a synergistic effect in combination with carbon-ion irradiation in radioresistant NMT-1R cells. However, there was no enhancement effect in radiosensitive NMT-1 cells. On the other hand, cisplatin had no enhancement in both cell lines. The increase in amount of apoptosis and the inhibition of Ku70 protein expression were found in the combination of carbon-ion irradiation and etoposide in NMT-1 cells. Conclusion: Etoposide might be effective for radioresistant tumors in combination with carbon-ion irradiation.