[Cytotoxic activities of Celecoxib on leukemic cells and the synergistic effects of Celecoxib with Imatinib thereupon].
OBJECTIVE
To explore the effects of Celecoxib on cell growth, early apoptosis, PRb and P27(Kip) protein expression of human leukemic cells of the line K562 and to determine its synergistic effects in combination of Imatinib.


METHODS
K562 cel1s were incubated with Celecoxib of the concentrations of 0, 10, 20, 40, 80, and 160 micromol/L for 36 hours, the cell vitality was determined by MTT assay, the early apoptosis was examined by flow cytometry (FC). The percentage of annexin V positive was detected by FC so as to evaluate the early apoptosis. The expression of PRb and P27(Kip) protein was detected by Western blotting. Another K562 cells were incubated with Celecoxib of the concentration of 40 micromol/L, Imatinib of the concentration of 0.2 micromol/L, or Celecoxib 40 micromol/L + Imatinib 0.2 micromol/L for 36 hours. Then the cell vitality and early apoptosis of the cells were detected so as to evaluate the synergistic effects of the combination of Celecoxib and Imatinib.


RESULTS
Celecoxib inhibited the K562 cells vitality significantly in a dose-dependent manner. The apoptotic rate of K562 cells was elevated with the increasing Celecoxib concentration. Celecoxib down-regulated the expression of PRb protein and up-regulated the expression of P27(Kip) protein in the K562 cells. The combination of Celecoxib and Imatinib exhibited evidently synergistic effects in terms of anti-proliferation on K562 cells.


CONCLUSIONS
Celecoxib inhibits the proliferation and induces apoptosis on leukemic cells in a dose-dependent fashion. The anti-proliferation effect of Celecoxib may be associated with the down-regulation of PRb expression and up-regulation of P27(Kip) expression. Combination of Celecoxib and Imatinib has obviously synergistic effects in terms of anti-proliferation on K562 cells.
Li
Rui-juan
RJ
Department of Hematology/Institute of Molecular Hematology, Second Xianya Hospital, Central South University, Changsha 410011, China.
Gong
Fan-jie
FJ
Zhang
Guang-sen
GS
D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis; D004357:Drug Synergism; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D010879:Piperazines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
D001549:Benzamides; D010879:Piperazines; D011720:Pyrazoles; D011743:Pyrimidines; D013449:Sulfonamides; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000068877:Imatinib Mesylate; D000068579:Celecoxib