Abstract
Indomethacin (IN) can inhibit cyclooxygenase activity and is considered to exert antitumor action in a variety of cancer cells. In the present study, we investigated the underlying mechanism of its antiproliferative effect on chronic myeloid leukemia (CML) cells. We studied the role of signal transducer and activator of transcription 1 or 5 (STAT1 or STAT5) and Bcl-XL proteins in IN-induced proliferative inhibition on CML cells. Both K562 cells and fresh bone marrow mononuclear cells from five CML patients were exposed to IN. Cell proliferation was determined by MTT assay. The expression of JAK2, STAT1, STAT5, and Bcl-XL proteins was probed with Western blotting. The level of phosphorylated STAT1 (p-STAT1) or STAT5 (p-STAT5) proteins was determined by coimmunoprecipitation combined with Western blotting. Intracellular localizations of both STAT1/STAT5 and p-STAT1/p-STAT5 were observed by indirect immunofluorescence assay. Our results showed that IN could inhibit the proliferation of CML cells in a dose-dependent manner (36–288 μg/ml). The expression of STAT1 and STAT5 was suppressed by IN both in a concentration-dependent manner and a time-dependent (0–36 h) manner. The levels of p-STAT1 and p-STAT5 were down-regulated by IN. A similar result was obtained for Bcl-XL protein expression. The intracellular fluorescence signals representing STAT1/STAT5 and p-STAT1/p-STAT5 were obviously weakened by IN. In contrast with IN, granulocyte-macrophage colony-stimulating factor could significantly promote the growth of CML cells and up-regulate the expression of both STAT1/STAT5 and p-STAT1/p-STAT5. This data indicated that IN is able to suppress the proliferation of CML cells, and the mechanism is associated with the inhibition of STATs/ Bcl-XL signal transduction pathway.
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This study was supported in part by the China Medical Board Grant No. 99–698.
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Zhang, G., Fu, Y. Antiproliferative effect of indomethacin on CML cells is related to the suppression of STATs/Bcl-XL signal pathway. Ann Hematol 85, 443–449 (2006). https://doi.org/10.1007/s00277-006-0098-0
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DOI: https://doi.org/10.1007/s00277-006-0098-0