Objective: To investigate the inhibition effect of arsenic trioxide (AS(2)O(3)) on the growth of human MDS-RAEB cell line MUTZ-1 cells and to explore the possible cellular and molecular mechanisms.
Methods: The apoptosis and differentiation of MUTZ-1 cells induced by AS(2)O(3) solution of different concentrations were studied with cell morphology, MTT, DNA fragmentation assay, RT-PCR, Nitroblue tetrazolium (NBT) reduction method and flow cytometry.
Result: (1) Low concentration ofAS(2)O(3) (0.05 - 0.25 micromol/L) had no marked growth inhibition effect on MUTZ-1 cells; after 14 d treatment, it down-regulated the expression of positive cell differentiation antigens CD38, CD7, CD10, HLA-DR (P<0.05), but did not up-regulate the expression of CD11b (P>0.05). (2) After treatment with 1.0 - 20.0 micromol/L of AS(2)O(3), MUTZ-1 cells presented typical features of apoptosis with a dose dependent manner (r=-0.999, P<0.05). The expression of bcl-2 mRNA and the ration of bcl-2/bax were decreased after AS(2)O(3) treatment (P<0.05).
Conclusion: Low concentration of (2)O(3) may have partial differentiation inducement on MUTZ-1 cells. With a certain range of dose (1.0 - 20.0 micromol/L), (2)O(3) can induce apoptosis of MUTZ-1 cells. (2)O(3) can significantly down-regulate bcl-2 and it might be one of the mechanisms of (2)O(3) treatment.