[Effect of celecoxib on enhancing the chemotherapic sensitivity of hydroxyurea to K562 cells and its mechanism].
OBJECTIVE
To determine whether celecoxib can enhance the anti-proliferative effect of hydroxyurea on K562 cells and to reveal its molecular mechanism.


METHODS
K562 cells were treated with low dose celecoxib (40 micromol/L) or hydroxyurea (10 mmol/L) and celecoxib (40 micromol/L) combined with hydroxyurea (10 mmol/L) for 36 h. The effects of the drugs on K562 cell growth inhibitation, apoptosis inducement and its molecular mechanism were analyzed by MTT assay, DNA fragment analysis, Western blotting, and RT-PCR.


RESULTS
The treatment of celecoxib (40 micromol/L) combined with hydroxyurea (10 mmol/L) could significantly inhibit the K562 cell viability and induce the K562 cell apoptosis than those treatments of celecoxib or hydroxyurea alone. The combination of celecoxib and hydroxyurea could evidently inhibit the expression of COX-2 protein or COX-2 mRNA of K562 cells.


CONCLUSIONS
Celecoxib can enhance the anti-proliferative effect of hydroxyurea on K562 cells, which is associated with the down-regulation of both COX-2 protein and COX-2 mRNA on K562 cells.
Liu
Ding-sheng
DS
Division of Hematology, lnstitute of Molecular Hematology,Second Xiangya Hospital, Central South University, Changsha 410011, China.
Zhang
Guang-sen
GS
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D020014:K562 Cells; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology*
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D006918:Hydroxyurea