Bcl-XL siRNA sensitisizes cisplatin-resistant human lung adenocarcinoma cells A549 to cisplatin

AIM: To investigate the effect of Bcl-XL siRNA on apoptosis and drug sensitization in cisplatin-resistance human lung adenocarcinoma cell line A549/DDP and to determine the inhibitory effect of the Bcl-XL siRNA on the expression of Bcl-XL gene in cells A549/DDP.METHODS: Bcl-XL siRNA and negative siRNA plasmid vector were stably transfected into A549/DDP cells.Drug sensitivity of the cells to cisplatin(DDP) was analyzed with MTT and flow cytometry.Spontaneous apoptosis of cells was detected by AO/EB dyeing.RTPCR and Western-blot were used to detect the target gene expression.RESULTS: MTT results showed that Bcl-XL siRNA transfectants had a higher cell inhibition rate than negative siRNA or untreated cells after treated with 0.2,2,20,200 μg/mL DDP.Moreover,flow cytometry results demonstrated that Bcl-XL siRNA cells had increased apoptosis rate after addition of 20 μg/mL DDP.Spontaneous apoptosis of cells were significantly increased in Bcl-XL siRNA stable transfectants.The mRNA and protein expression level of Bcl-XL in Bcl-XL siRNA stable transfectants were obviously reduced compared with negative siRNA transfectants or untreated cells,moreover,Bcl-XL siRNA increased the activity of active caspase-3.CONCLUSION: siRNA targeting Bcl-XL gene can specifically down-regulate Bcl-XL expression in A549/DDP cells,increase cell spontaneous apoptosis and sensitize cells to DDP.Bcl-XL siRNA may be a potential therapy agent against human lung adenocarcinoma.