Radiobiological effects of irradiation plus olaparib with different dose rates on CNE-2 cell line / 中华放射肿瘤学杂志

ABSTRACT

Objective To investigate the radiobiological effects of radiation with different dose rates on human nasopharyngeal carcinoma cell line CNE-2 treated with or without a poly ADP-ribose polymerase (PARP) inhibitor,olaparib.Methods The concentration of olaparib used to treat cells equaled to the inhibition concentration IC10 of olaparib to CNE-2 cells.The CNE-2 cells were divided into acute radiotherapy (RT) group,fractionated radiotherapy (FRT) group,olaparib + RT group,and olaparib + FRT group.All groups were exposed to radiation of 0,1,2,3,5,7,and 10 Gy at a dose rate of 3 Gy/min.The delivery time for each dose point was 4 min in RT and 30 min in FRT.The colony forming assay was used to evaluate the survival of CNE-2 cells at each dose point.The multi-target,single-hit model was used to fit the cell survival curves and the parameters,D0,Dq,and SF2,were calculated.At dose points of 0.1,and 2 Gy,western blot was used to determine the expression of PARP-1 in the RT group and the FRT group and γH2AX in each group.Immunofluorescence was used to evaluate the γH2AX focus formation.A single factor analysis of variance was used to compare the 4 groups,and two two compared with SNK-q test.Results The IC10 value of olaparib to CNE-2 cells was 4.0 μmoL/L.At dose points of 1 and 2 Gy,the PARP-1 expression was significantly higher in the FRT group than in the RT group (P=0.029,0.022),while the γH2AX focus number was significantly smaller in the FRT group than in the other three groups (all P＜0.05);compared with the RT group,the D0,Dq,and SF2 values in the FRT group were increased by 11.67％,15.78％,and 23.61％,respectively;compared with the FRT group,the D0,Dq,and SF2 values in the Olaparib+ FRT group decreased by 11.19％,6.44％,and 13.26％,respectively;there were no significant differences in above indices between the RT group,the Olaparib+RT group,and the Olaparib+FRT group.Conclusions For the same radiation dose,fractionation reduces the relative dose rate and weakens the radiobiological effects.lowdose olaparib can compromise the single strand break repair induced by the decline of the relative dose rate in a fractionated irradiation mode,which promotes the formation of double-strand break and improves the radiobiological effects.