<br> Pre radiation sorafenib treatment had no effect on the formation of DNA DSB

<br> Pre radiation sorafenib treatment had no effect on the formation of DNA DSBs, but promoted repair of DNA KU-0063794 ic50 damages, which could lessen the chance of mitotic catastrophe. DNA dam age had been almost completely repaired in the irradiated hepatocellular carcinoma cells since less than 5% of the irradiated cells contained significant DNA damage. We speculate that post irradiation sorafenib did not increase repair of DNA damages in HCC. The dis tinct effects on DNA repair by the two schedules of sora fenib may partially explain the enhanced HCC viability with pre irradiation sorafenib compared to the lower cell viability in irradiated HCC samples treated with sorafenib 24 post radiation. The activation of cell cycle checkpoints plays a signifi cant role in the DNA damage response.<br><br> It prevents damaged cells from entering the next phase of the cell cycle. Prolonged G2 arrest Lenalidomide ic50 appears to contribute to the ability of the cell to survive radiation. As expected, we found that irradiation induced the activa tion of the G2M checkpoint in hepatocellular carcin oma cells at 16 h post irradiation. Additionally, we observed that pre irradiation sorafenib delayed the onset of the G2M checkpoint, which could allow more time for the irradiated hepatocellular carcinoma cells to repair DNA damages. Our clonogenic assays showed that sora fenib given prior to irradiation rendered hepatocellular carcinoma cells more radio resistant, which could be due to the delayed onset of the G2M checkpoint, allow ing the irradiated cells more time to repair DNA damages.<br><br> As expected, HCC cells treated with post irradiation sorafenib LY294002 構造 had no effect on the G2M peak at 16 hrs post radiation. As the current study was carried out in vitro, we did not examine the anti angiogenic effect of sorafenib on radio sensitivity in hepatocellular carcinoma cells. We found that sorafenib exerts a schedule dependent effect on HCC radio sensitivity, which could be of significance for the treatment of hepatocellular carcinoma patients with sorafenib in combination with adjuvant radiother apy. Our findings suggest that the efficacy of sorafenib based therapy in combination with radiotherapy may depend on the timing of sorafenib administration rela tive to that of radiotherapy. On the basis of our in vitro studies, we speculate that post irradiation sorafenib could be more effective in potentiating tumor inhibitory effect of radiotherapy.<br><br> Further studies are needed to confirm this schedule dependent effect of sorafenib in animal models bearing human hepatocellular carcinoma xenografts and in clinical studies. Conclusions Sorafenib combined with irradiation exerted a schedule dependent effect in HCC cells in vitro. Sorafenib given 30 min prior to irradiation reduced the anti proliferative effects of irradiation against HCC whereas sorafenib given 24 hr after irradiation increased the anti tumor effects against HCC. These results have significant impli cations for the combined use of sorafenib and radiother apy against HCC in the clinic. Background Colorectal cancer is the third most common tumour in the world, with over 1.