[Proliferation inhibition effect of indomethacin on CML cells associated with down-regulation of phosphorylated STAT1/STAT5 and inhibition of COX-2 expression].
OBJECTIVE
To explore the mechanism of anti-proliferative effect of indomethacin (IN) on chronic myelogenous leukemia (CML) cells.


METHODS
MTT was applied to assay CML cells viability under IN intervention. STAT1, STAT5 proteins were analyzed by Western blot, the expressions of phosphorylated STAT1 or STAT5 by immunoprecipitation combined with Western blot, the cellular localization of p-STATs proteins by indirect immunofluorescence technique, and the detection of Bcl-X(L) and COX-2 protein by Western blot.


RESULTS
IN could significantly inhibit the viability of CML cells. 0 approximately 400 micromol/L of IN could down-regulate the expression of p-STAT1 or p-STAT5 in a dose-response manner, p-STATs were distributed mainly in the nucleus as scattering spots. The expression of COX-2 protein could be detected in K562 cells. Both Bcl-X(L) and COX-2 proteins could be inhibited by IN in a dose-dependent manner.


CONCLUSIONS
IN could significantly inhibit the proliferation of CML cells, the mechanism of which might be related to the suppression of STATs/Bcl-X(L) signal transduction pathway. There exists COX-2 protein expression in K562 cells, the anti-leukemia effect of IN was possibly dependent on COX-2 pathway.
Zhang
Guang-sen
GS
Institute of Molecular Hematology, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
Fu
Yun-bi
YB
Xia
Meng
M
D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D010766:Phosphorylation / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050799:STAT5 Transcription Factor; D051020:bcl-X Protein; D051546:Cyclooxygenase 2; D007213:Indomethacin