Radiosensitivity Mechanism Of Oxaliplatin On The Non-small Cell Lung Cancer Cell Line A-549

Purpose:To explore the enhancing radiosensitivity of oxaliplatin on human Non-small Lung Cancer cell A549 to providing the theoretical evidence to improving treatment of tumor by radiation.Methods :The Non-small Lung Cancer cell A549 were put into four groups randomly.Two of the groups were effected only by oxaliplatin or radiation, one was effected by radiation with different doses(1,1.4,1.8,2,3Gy) and same oxaliplatin dose(IC10),or the same radiation dose(2Gy) and different oxaliplatin doses(0.488,0.244,0.122,0.061,0.031μg/mL).The last one was control group. Observing result with MMT method, calculating the suppression rates and SER (sensitization enhancement ratio).The effects of L-OHP combining radiation were also tested by clonogenic assay, using IC10 concentration of L-OHP and different doses of radiation."Multi-target single hit survival model"(SF=1-(1-e-D/D0)N)) was used for dealing with data,then built the cell surviving curve.Cell cycle and apoptosis percentage were detected with flow cytometry.All data were dealt with ANOVA test, multiple correlation with the software SPSS13.0.Results :(1)The impact of non-small cell lung cancer A549 cell line by oxaliplatin:With the increase in the concentration of oxaliplatin, the cell survival rate decreased.When the oxaliplatin concentration was 0.488μg/mL, its inhibition was less than 10%,and survival rate was 91.39±0.878.So we took 0.488μg/mL as the best experimental concentration of oxaliplatin.(2)MTT suppression experiment:Flown the OD value of many group which effected by different doses of radiation,we knew drug combined radiation group significantly had higher suppression rate of tumor cells than the control group.And higher rates of tumor inhibition as radiation dose increased (between groups F=272.964,P<0.001; range groups F=33.883,P<0.001). The A549 cells with different oxaliplatin doses also had a statistically difference (F=8.871, P<0.001),higher drug concentration on the higher suppression rate of A549 cells.(3)Radiosensitization ratio analysis:Oxaliplatin could enhance radiation on A549 cells,the sensitizing enhancement ratio was up to 2.791 (P=0.009).And radiosensitivity showed positive correlation with radiation dose and drug concentration (P=0.002).(4)Analasis of clone formation: Dq,SF2 values of L-OHP+radiation group were lower than the radiation group, suggesting that L-OHP could significantly enhanced the radiosensitivity of A549 cells.(5)The result of the flow cytometry: Oxaliplatin enhanced the radiosensitivity by increasing the number of G2/M phase.Conclusions :Oxaliplatin can enhance the radiosensitivity of Non-small Lung Cancer cell lines A549.It enhanced radiosensitivity of G2/M phase.