Abstract: Sorafenib Decreases the Anti-tumor Effect of Radiation in Hepatocelluar Carcinoma in vitroQiaoqiao LI , Mengzhong LIU, LiWANG, Jinqing LICorrespondence to: Mengzhong LIU, E-mail: liumz@sysucc.org.cnDepartment of Radiation Oncology, Cancer Center of Sun Yat-sen University, Guangzhou 510060, ChinaAbstract Objective: To observe the effect of radiation combined with Sorafenib on hepatocellular carcinoma cells. Methods: Humanhepatocellular carcinoma cell ( HCC ) lines SMMC-7721 and BEL-7402 were studied. One set was treated with radiation alone ( IR group )and the other set was treated with Sorafenib followed by radiation (IR+S group). Acolony-forming assay was performed with the cell fractionsthat survived radiation with and without Sorafenib and the sensitivity enhancement ratio was calculated. The MTS assay was used to compareproliferation in the 2 groups after treatment. Flow cytometry was used to quantify apoptotic cells and cell cycle distribution. The tumor cellswere irradiated and their DNA double stranded breaks ( DSbs ) were detected through γ-H2AX focus by immunofluorescence. Results: TheIR+S treated HCC cells formed more colonies. The sensitivity enhancement ratio (SERSF2) was 0.78 in the IR+S treated SMMC-7721 cellsand 0.88 in the IR+S treated BEL-7402 cells. Curve analysis with data from the MTS assay showed that the inhibition in the IR+S groupwas similar to that in the IR group at 2 days after radiation. Sorafenib increased the apoptotic cells at 24 hours after radiation. The proportionof apoptotic cells in the IR+S set was 18.3%±2.0%, while the proportion in the IR set was 6.1%±1.0% in SMMC-7721 cells. The proportionof apoptotic cells in the IR+S set was 17.0%±2.4%, while the proportion in the IR set was 8.2%±2.1% in BEL-7402 cells ( P < 0.05.).Sorafenib had no effect on the proportion of apoptotic cells at 48 h ours after radiation. Sorafenib delayed and prolonged the arrest of cellsin G2/M. The percentage of cells positive for DNA damage was similar in the two groups at 30 hours after radiation but was higher in theIR group than in the IR+S group at 6 hours after radiation. The proportion of cells with DNA damage in the IR+S group was 23.8%±2.9%,while the proportion in the IR group was 59.9%±2.4% in SMMC-7721 cells. The proportion of cells with DNAdamage in the IR+S set was25.0±3.0%, while the proportion in the IR set was 46.4%±3.8% in the BEL-7402 cells ( P < 0.001). Conclusion: Pre-radiation Sorafenibdecreases the effect of radiation on HCC cells. Further studies in vivo are required to consider more suitable combinations to increase theradiation effect on HCC cells.Keywords Hepatocellular carcinoma; Radiation; Sorafenib