Resumo

WU, Yuni et al. Tetramethylpyrazine potentiates arsenic trioxide activity against HL-60 cell lines. Braz J Med Biol Res [online]. 2012, vol.45, n.3, pp. 187-196.  Epub 16-Fev-2012 ISSN 1414-431X.  http://dx.doi.org/10.1590/S0100-879X2012007500017.

The objective of this study was to evaluate the effects of tetramethylpyrazine (TMP) in combination with arsenic trioxide (As₂O₃) on the proliferation and differentiation of HL-60 cells. The HL-60 cells were treated with 300 µg/mL TMP, 0.5 µM As₂O₃, and 300 µg/mL TMP combined with 0.5 µM As₂O₃, respectively. The proliferative inhibition rates were determined with MTT. Differentiation was detected by the nitroblue tetrazolium (NBT) reduction test, Wright’s staining and the distribution of CD11b and CD14. Flow cytometry was used to analyze cell cycle distribution. RT-PCR and Western blot assays were employed to detect the expressions of c-myc, p27, CDK2, and cyclin E1. Combination treatment had synergistic effects on the proliferative inhibition rates. The rates were increased gradually after the combination treatment, much higher than those treated with the corresponding concentration of As₂O₃ alone. The cells exhibited characteristics of mature granulocytes and a higher NBT-reducing ability, being a 2.6-fold increase in the rate of NBT-positive ratio of HL-60 cells within the As₂O₃ treatment versus almost a 13-fold increase in the TMP + As₂O₃ group. Cells treated with both TMP and As₂O₃ expressed far more CD11b antigens, almost 2-fold compared with the control group. Small doses of TMP potentiate As₂O₃-induced differentiation of HL-60 cells, possibly by regulating the expression and activity of G0/G1 phase-arresting molecules. Combination treatment of TMP with As₂O₃ has significant synergistic effects on the proliferative inhibition of HL-60 cells.

Palavras-chave : Tetramethylpyrazine; Acute promyelocytic leukemia; Arsenic trioxide; HL-60 cell; Proliferation; Differentiation.