[Indomethacin-induced HL-60 cell apoptosis is associated with inhibition of beta-catenin/c-myc signal transduction pathway].
OBJECTIVE
To investigate the effects of indomethacin on HL-60 cell proliferation and apoptosis, and elucidate partly the molecular mechanism about the anti-leukemia effect of indomethacin by studying beta-catenin signal transduction pathway.


METHODS
HL-60 cells were treated with indomethacin at different concentrations (0, 25, 50, 100, 200, 400 micro mol/L). Cells viability and proliferation were determined by Trypan blue staining and cell counting respectively. DNA ladder pattern and cell morphology were used to identify cell apoptosis. The expression and cleavage of caspase-3, beta-catenin, c-myc were detected by Western blot techniques.


RESULTS
Indomethacin could significantly inhibit HL-60 cells proliferation and induce cells apoptosis with a time and dose dependent manner. An up-regulating expression and cleavage of caspase-3 were observed. Indomethacin could inhibit beta-catenin expression and induce its degradation, c-myc protein exhibited a down-regulation with a concentration dependent manner.


CONCLUSIONS
Indomethacin could inhibit HL-60 cell proliferation and induce cells apoptosis. Anti-leukemia effect of indomethacin was associated with the inhibition of "beta-catenin --> c-myc" signal pathway.
Zhang
Guang-sen
GS
Division of Hematology, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
Wang
Zhao-yi
ZY
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
D000894:Anti-Inflammatory Agents, Non-Steroidal; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators; D051176:beta Catenin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D007213:Indomethacin