Inhibition effect of fludarabine on the growth of myelodysplastic syndrome cell line MUTZ-1 and its mechanism

OBJECTIVE: To investigate the inhibition effect of fludarabine on the growth of human MDS-RAEB cell line MUTZ-1 and to explore the possible cellular and molecular mechanism. METHODS: The apoptosis of MUTZ-1 cells induced by fludarabine was studied by transmission electron microscope, MTT assay, DNA ladder test, flow cytometry and RT-PCR method. RESULT: Treatment with fludarabine remarkably inhibited the growth of MUTZ-1 cells, the 24 h IC(50), 48 h IC(50) and 72 h IC(50) of fludarabine for MUTZ-1 cells were 137.65 mg/L, 6.27 mg/L and 0.51 mg/L, respectively. Fludarabine inhibited the growth of MUTZ-1 cells in a dose-dependent and time-dependent manner. After treated by fludarabine (1 mg/L-16 mg/L)for 24 h, MUTZ-1 cells showed the typical features of apoptosis. After fludarabine treatment the mRNA expression of Bcl-2, Bax, survivin, XIAP, cIAP-1 and cIAP-2 was not changed, but the mitochondrial membrane potential (MMP) was decreased. CONCLUSION: With a certain range of dose fludarabine (1 mg/L-16 mg/L)could inhibit MUTZ-1 cell growth by inducing cells apoptosis. MMP may play a certain role in apoptosis of MUTZ-1 cells induced by fludarabine.