Effect Of Simvastatin On Proliferation And Apoptosis Of Non-small Cell Lung Cancer A549 Cells And Its Mechanism

Objective: To study the effect of simvastatin on the proliferation of non-small cell lung cancer A549 cells and its mechanism of action.Methods: A549 cells were cultured in vitro.CCK-8 assay and flow cytometry assay were used to observe the effects of simvastatin on proliferation and apoptosis of A549 cells;Hoechst33528 fluorescence staining were used to observe the changes of cell morphology after drug treatment;Western blot was used to detect the effect of simvastatin on the expression of XIAP,Caspase-3 and GRP78 in A549 cells.Result:(1)Simvastatin treatment of non-small cell lung cancer A549 cells for 24 hours,using CCK-8 assay,the results showed that 30?mol / L,40?mol / L simvastatin cell group,the proliferation activity was significantly lower than the untreated group(P <0.01),result has statistical significane;After 48 hours of treatment,the activity of each simvastatin group was lower than that of the untreated group(P <0.05),with statistical significance;Compared with the untreated group,the cell viability in each group was significantly decreased(P <0.01)at 72 hours,the difference was statistically significant;(2)Hoechst33528 fluorescence staining showed that after simvastatin treatment of A549 cells,the cell morphology showed a typical apoptotic changes,manifested as cell shrinkage and chromatin condensation of dense chromatin appeared dense,and the cell color turns white.With the increase of drug concentration,the apoptotic state was more obvious(P <0.01).(3)Flow cytometry was used to detect the apoptotic rate in each group.The results showed that the apoptotic rate of 20 ?mol / L simvastatin group and 40 ?mol / L group were significantly higher than that of the control group(P <0.01).(4)Western-blot showed that the expression of Caspase-3 and GRP78 protein in simvastatin group was significantly higher than that in untreated group(P <0.01),and XIAP protein expression was significantly lower than that in untreated group(P <0.01),result has Statistical differences.Conclusion:(1)Simvastatin inhibits the proliferation of non-small cell lung cancer A549 cells,induces apoptosis and presents typical apoptotic morphology?(2)After simvastatin treatment,Caspase-3 and GRP78 protein expression levels were up-regulated,while XIAP protein expression was decreased,This confirms that simvastatin induced the apoptosis of A549 cells by acting on the inhibition of XIAP protein expression and reducing the inhibition of Caspase-3 protein,activate Caspase apoptosis pathway and Activate GRP78 protein-mediated endoplasmic reticulum apoptosis pathway to play a role.