[Celecoxib promotes apoptosis of breast cancer cell line MDA-MB-231 through down-regulation of the NF-kappaB pathway].
OBJECTIVE
Celecoxib can inhibit cell proliferation, regulate cell cycle and induce apoptosis, but the underlying mechanisms are still unclear. This study was to investigate the association between the NF-kappaB (kappaB) pathway and the apoptosis of breast cancer cell line MDA-MB-231 induced by celecoxib.


METHODS
The expression of cyclo-oxygenase-2 (COX-2) mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Cell proliferation and cell cycle were detected by MTT and flow cytometry (FCM), respectively. The protein expressions of caspase-3 and p65 in MDA-MB-231 cells were detected by western blot.


RESULTS
After incubation with different concentrations of celecoxib for 48 h, COX-2 mRNA expression in MDA-MB-231 cells was decreased in a dose-dependent manner compared with untreated cells (P<0.05). Proliferation of MDA-MB-231 cells was reduced drastically in a dose-and time-dependent manner after celecoxib treatment (P<0.05). Combination of prostaglandin E2 (PGE2) and celecoxib exerted similar inhibition effect to celecoxib alone on cell growth (P>0.05). High-dose celecoxib induced an increase in the percentage of G0/G1 phase cells accompanied by the change in DNA ploidy. The cellular caspase-3 level was enhanced whereas the p65 level was decreased in celecoxib-treated MDA-MB-231 cells after 24 h in comparison to those in the control cells.


CONCLUSIONS
Celecoxib could inhibit MDA-MB-231 cell proliferation and promote cell apoptosis by down-regulating the NF-kappaB signaling pathway.
Wang
Ling
L
Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, P. R. China. wangling1981@yahoo.com.cn
Liu
Li-Hong
LH
Shan
Bao-En
BE
Zhang
Chao
C
Sang
Mei-Xiang
MX
Li
Jia
J
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D006801:Humans; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism*
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; C498143:RELA protein, human; D012333:RNA, Messenger; D013449:Sulfonamides; D051996:Transcription Factor RelA; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; D000068579:Celecoxib; D015232:Dinoprostone