Abstract: OBJECTIVE:This study aimed to investigate whether Fludarabine,at a low-concentration, would enhance induction of apoptosis in A549 cells by TRAIL. METHODS: A549 cultures were organized into different groups:control, Fludarabine, TRAIL, and Fludarabine plus TRAIL. The CCK-8 method was used to detect effect of Fludarabine and/or TRAIL on A549 and human umbilical vein endothelial cells (HUVEC). Flow cytometry was used to detect apoptosis rates. Western Blot was used to detect apoptosis-related proteins Survivin,Bcl-2,Bcl-xl,caspase-8,caspase-3,and the expression of JNK and p38. RESULTS: Fludarabine(25 or 50 μmol/L) or TRAIL alone had no significant effects on viability of A549 and HUVEC cells, or apoptosis in A540 cells. The inhibition rates from combined treatment of Fludarabine (25 or 50 μmol/L) and TRAIL were 30.9% and 44.9%, respectively, in A549 cells and the effect was concentration dependent. The combined treatment also caused apoptosis in 89.3% of A549 cells, as well as decreased expression of Survivin,Bcl-2 and Bcl-xl,promoted the activation of caspase-8 and caspase-3,and promoted the phosphorylation of JNK and p38. CONCLUSION:Fludarabine combined with TRAIL specifically induced apoptosis in A549 cells.

Key words: Fludarabine, tumor necrosis factor-related apoptosis-inducing ligand, A549, apoptosis