Relationship between survivin and paclitaxel in human lung cancer cell lines

Objective:To explore the relationship between survivin and paclitaxel in human lung cancer cell line A549.Methods:A549 cells were exposed to paclitaxel,then the growth inhibiting effects of the cell line were determined by MTT assay,the change of the cell cycle and apoptosis were analyzed with flow cytometry and the protein expressions of survivin were detected by Western blot.Results:The effects of paclitaxel on the cells had time characteristics.The growth rate of cells exposed to paclitaxel began to slow at 12h,and this effect was significantly time-dependent(P0.05).Paclitaxel of different concentrations also had different effects on the cell line(P0.05).At one time,the higher concentration of paclitaxel,the lower survival rate of cell.At the time-dependent experiment,10nM paclitacxel rapidly up-regulated survivin expression and resulted in G2/M arrest within 4h in A549 cells.Lengthening paclitaxel treatments(48h or more) significantly attenuated survivin induction and G2/M arrest in comparison with the early times.But paclitaxel-induced apoptosis had another changing form,a positive correlation with treatment time.At the concentration-dependent experiment,low concentrations of paclitaxel induced survivin as effectively as high concentration ones did,and the cells showed the time-dependent G2/M arrest(P0.05) and the highest apoptosis at 10nM.Survivin expression had no relationship with G2/M arrest or apoptosis.Conclusion:Paclitaxel inhibits the growth of A549 cells in vitro in time-dependent manner.Different concentrations paclitaxel also have different effects on the cells,and the relationship between survivin and G2/M arrest and apoptosis may be distinct at different drug concentrations.10nM-paclitaxel-mediated survivin expression showed a similar changing trend with G2/M arrest and an opposite direction with apoptosis at the time-dependent experiment.These suggested that the mitotic survival pathway may be at least one means involving survivin by which lung cancer cells counteract paclitaxel induced apoptosis following drug treatment.Targeting this survival pathway may result in novel approaches to enhance the responsiveness of lung cancer to paclitaxel.