Effects of paclitaxel on proliferation and apoptosis in human acute myeloid leukemia HL-60 cells.

Acta Pharmacol Sin

Department of Pharmacology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Published: March 2004

Aim: To investigate the regulatory effect of paclitaxel on proliferation and apoptosis in human acute leukemia HL-60 cells.

Methods: HL-60 cell growth was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tertrazolium bromide (MTT) colorimetric assay. Cell cycle kinetics and apoptosis were analyzed by flow cytometry and microscopic examination. In addition, DNA microarrays containing 14,400 EST elements were used to investigate the gene expression pattern of HL-60 cells exposed to paclitaxel 1 micromol/L.

Results: Paclitaxel inhibited HL-60 cell growth significantly in a dose-dependent and time-dependent manner (P<0.01). Marked cell accumulation in G2/M phase and multinucleated cells were also observed after treatment with paclitaxel 0.1 and 1 micromol/L. Among 14400 EST elements, 277 genes were found to be markedly up- or down-expressed in the HL-60 cells treated with paclitaxel 1 micromol/L for 0.5 h, comprising 210 known genes and 67 unknown genes.

Conclusion: Paclitaxel suppresses the growth of HL-60 cells in vitro by causing cell-cycle arrest and apoptosis. The results of microarray suggest that paclitaxel initiates apoptosis through multiple mechanisms.

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