Resveratrol Enhance Irradiation Sensitivity Of Lung Adenocarcinoma Via Suppression Of Store Operated Calcium Entry In A549 Cells

Objective To study the effect of resveratrol enhance lung adenocarcinoma A549 cells irradiation sensitivity,and to explore whether it regulates Store-operated calcium entry(SOCE)to achieve sensitization effect by affecting Stim and / or Orai expression.To provide research basis for improving the irradiation sensitivity effect and prognosis of patients with advanced lung cancer.Method Lung adenocarcinoma A549 cells were subcultured,and they were treated with different irradiation doses(0,2,4,6 Gy)combined with different concentrations of resveratrol(0,10,50,100,150,200 ?mol / L).Cell counting and observation,CCK8 detection and mitochondrial membrane potential were used to compare cell death before and after treatment.Analyzed these results to select the optimal dose group,setted up a single treatment group and a blank control group.the expression levels of STIM1,Orai1 and STIM2,Orai2 and Orai3 in the cells before and after treatment were detected by Western blot.And used calcium imaging technology to detect phytotoxicity-induced Store-operated calcium entry(SOCE).In addition,constructed vectors and used overexpression technology to verify these results.Result 1.Through cell counting and observation,CCK8 detection,mitochondrial membrane potential measurement,it was found that Res combined radiation can induce more significant cell death than radiation alone,this relationship is dose-dependent.And resveratrol 100 ?mol / L combined with irradiation dose 4 Gy is the Optimal combination with the most cell death and the smallest dose.2.Res combined with irradiation dose-dependently reduced the expression of STIM1 and Orai1 in A549 cells,but had no significant effect on STIM2,Orai2 and Orai3.3.Compared with single treatment,Res combined with irradiation can inhibit Store-operated calcium entry(SOCE)induced by thapsigargin(TG)in A549 cells.4.Overexpression of STIM1 and Orai1 can reverse Res-induced SOCE inhibition and reduce A549 cell death caused by resveratrol combined with irradiation.Conclusion Res can significantly enhance the effect of irradiation sensitivity on lung adenocarcinoma A549 cells,and this effect may be mediated by down-regulating the expression of STIM1 and Orai1 and inhibiting SOCE in the cell.