Abstract
Radiotherapy is now widely applied for the eradication of malignant tumors, however, the existence or outbreak of radioresistant cells is one of the major concerns in radiotherapy. In order to develop more effective radiotherapy, we have to understand the characteristics of radioresistant cells. Recently, we obtained a clinically relevant radioresistant cell line, HepG2-8960-R by exposure of HepG2 cells to long-term fractionated X-rays. These cells continue to proliferate even with the administration of daily exposure to 2 Gy of X-rays, that is, clinically relevant dose to the standard radiotherapy. In this study we examined the contribution of autophagy to radioresistance in vitro. After administration of fractionated 2 Gy of X-rays, autophagy was induced in HepG2 but not in HepG2-8960-R, suggesting that mTOR pathway is activated in radioresistant cells. Administration of mTOR inhibitor, rapamycin reverted radiosensitivity of HepG2-8960-R cells to the level of parental cells determined by high density survival assay. These strongly suggest that radiotherapy combined with the administration of rapamycin could be effective for the eradication of radioresistant cells.
