engleski

Antiproliferative effect of phosphatidylinositol 3-kinase inhibitor LY294002 on HL-60 and K562 leukemia cell lines

Background and Purpose:LY294002 is a cell-permeable, potent and specific phosphatidylinositol 3-kinase (PI3K) inhibitor which has been widely used to elucidate the cellular functions of PI3Ks activated in response to different agonists. The present study was undertaken in order to test for possible effects of long-term exposure to increasing concentrations of LY294002 inhibitor alone on the proliferation and cell cycle status of human leukemia HL-60 and K562 cell lines. Materials and Methods: HL-60 and K562 cells were plated at a cell density of 0.5x10^6/ml in RPMI medium containing 10% FBS in the presence of various doses of LY294002 or a vehicle alone.The cells were harvested at the indicated times and viable cells were determined by trypan blue exclusion and quantified using a hemocytometer. The expression of cell surface antigens was determined by flow cytometry using FITC-conjugated antihuman CD71, antihuman CD11b antibody or an appropriate isotype controls. The DNA content of cultured cells was exemined by staining with propidium iodide and analyzed using a FACSscan with a ModFit software. Results and Conclusions: The presence of increasing doses of LY294002 inhibited the growth of both HL-60 and K562 leukemia cells in liquid cultures to the similar level, decreased the level of transferrin receptor, and induce a decrease in the proportion of cells in the S-phase of the cell cycle with a parallel increase in the proportion of cells in G_0/G_1 and/or G_2/M phase. No significant change was observed in the percentage of cells in sub-G_0/G_1 phase at any dose tested. Therefore, we can conclude that the long-term presence of increasing doses of LY294002 has an antiproliferative effect on both HL-60 and K562 human leukemia

LY294002; phosphatidylinositol 3-kinase; leukemia; HL-60; K562; proliferation; cell cycle

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