[Proliferation-inhibiting effect of indomethacin on chronic myeliod leukemia cells is related to the supression of STAT signal transduction pathway].
This study was aimed to observe whether expressions of JAK2, STAT1, STAT5 proteins in indomethacin-treated CML cells involved in the proliferation inhibition of CML cells, and elucidate the pharmacological mechanism of indomethacin anti-leukemia. MTT assay and trypan blue dye exclusion test were used to detect the inhibitory effect of indomethacin on CML cells proliferation. JAK2, STAT1, STAT5 proteins were analyzed by Western blot; the subcellular distribution of STAT1, STAT5 were detected with indirect immunofluorescence technique. The results showed that indomethacin at >or= 400 micromol/L significantly inhibited the proliferation of CML cells and down-regulated the expression of STAT1, STAT5 protein, no JAK2 change was observed. STAT1 and STAT5 were located in cytoplasm. It is concluded that indomethacin inhibits the proliferation of CML cells and the mechanism may be related to down-regulated expression of STAT, or blockage of cells growth signals.
Fu
Yun-Bi
YB
Institute of Molecular Hematology, The Second Xiangya hospital, Central South University, Changsha 410011, China.
Zhang
Guang-Sen
GS
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D053614:Janus Kinase 2 / Q000378:metabolism; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000473:pathology; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050799:STAT5 Transcription Factor; D053614:Janus Kinase 2; D007213:Indomethacin