Objective: To explore the potential mechanisms of leukemia cell resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) -induced apoptosis.
Methods: Cells apoptosis, changes of mitochondrial membrane potential, activity of NF-kappaB, activity of caspase-8 and expressions of apoptosis-related proteins in TRAIL treated K562 and CEM cells, were detected by flowcytometry, ELISA and Western blotting methods, respectively.
Results: After treated with TRAIL, the apoptosis indexes were 29.98% and 14.1%, and mitochondrial membrane potential were decreased to 73.25% and 25.4% in K562 and CEM cells respectively. Constitutive level of caspase-8 expression in CEM was lower than that in K562 cells. Both cells became over-expressed Bcl-xL and down-regulated Bax. The ratio of Bcl-xL/Bax in CEM cells was higher than that in K562 cells. Compared with that in K562, the NF-kappaB activity increased significantly in CEM after treatment with TRAIL in early stage.
Conclusion: CEM cells were more resistant to TRAIL-induced apoptosis than K562 cells did. The potential mechanisms associated with CEM drug resistance might be the lower expression of the constitutive level of caspase-8, lower sensitivity of mitochondrial inner membrane, early increase in NF-KB activity and altered expression of Bcl-2 proteins family.