耐辐射肺腺癌细胞模型的放射生物学鉴定OA北大核心CSTPCD

AIM:To establish a radioresistant lung adenocarcinoma cell model in vitro and investigate the bio-logical changes related to radiation resistance in tumor cells.METHODS:A radioresistant lung adenocarcinoma cell model namely A549RR,was established by fractionated irradiation.The A549 and A549RR cells were randomly divided into two groups,which were irradiated with 0 and 8 Gy.The proliferation ability of parental cells and radioresistant cells were detected to assess their sensitivity to radiotherapy.The A549,A549RR and A549RR'(partially radioresistant)cell lines were divided into cisplatin chemotherapy group,cisplatin chemotherapy combined with radiotherapy group and blank control group to evaluate the sensitivity to chemotherapy and radiochemotherapy.Flow cytometry was used to detect the changes in cell cycle and apoptosis after irradiation,while the comet assay was used to evaluate DNA damage.The levels of reactive oxygen species(ROS)and 8-hydroxydeoxyguanosine(8-OHdG)levels were measured,and senescence-associ-ated β-galactosidase staining was performed.RESULTS:Compared with parental A549 cells,A549RR cells exhibited enhanced radiation resistance(P<0.01),decreased proliferation capacity(P<0.01),and no significant difference in cell viability before and after chemotherapy.In comparison to A549 cells,the proportion of A549RR cells at G2/M phase was significantly decreased(P<0.01),and that at S phase was significantly increased(P<0.01).After exposed to high-dose irradiation,A549 cells displayed S phase arrest,whereas A549RR cells showed no significant difference in cell cycle be-fore and after irradiation.Additionally,A549RR cells exhibited reduced DNA damage(P<0.01)and lower levels of ROS(P<0.01)compared with A549 cells following irradiation.There were no significant differences in the levels of 8-OHdG and apoptotic rate before and after irradiation in A549RR cells.CONCLUSION:In this study,by establishing a radia-tion-resistant cell model,the impact of radiotherapy on the survival of radioresistant lung cancer cells was investigated,as well as the corresponding changes in cell cycle progression,DNA damage,apoptosis,senescence,and oxidative stress levels.These findings are expected to contribute to a better understanding of the mechanisms underlying radiation resis-tance in lung cancer and may inform further research in this field.