JTE-522, a selective COX-2 inhibitor, inhibits cell proliferation and induces apoptosis in RL95-2 cells.
OBJECTIVE
To investigate whether JTE-522 [4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide], a selective COX-2 inhibitor, can induce apoptosis and inhibit cell proliferation in human endometrial cancer cell line RL95-2 cells and to explore the molecular mechanisms.


METHODS
[3-(4,5)-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT), DNA ladder, enzyme-linked immunosorbent assay (ELISA), flow cytometry, RT-PCR, and Western blot analysis were employed to investigate effect of JTE-522 on human endometrial cancer cell line RL95-2 cells and the related molecular mechanisms.


RESULTS
JTE-522 inhibited the growth of RL95-2 cells and induced the apoptosis. Furthermore, it arrested G0/G1 phase and inhibited S phase in RL95-2 cells. JTE-522 inhibited the expressions of COX-2 mRNA, phosphorylated Rb, and CDK4 proteins, while increased the levels of p53, p21, cyclin D1 proteins, and the activity of caspase-3 in RL95-2 cells.


CONCLUSIONS
JTE-522 inhibits cell proliferation and induces apoptosis in RL95-2 cells, which may be associated with the activation of caspase-3-like proteases, down-regulation of the expression of COX-2 mRNA, phosphorylated Rb, and CDK4 proteins, and up-regulation of the expressions of p53, p21, and cyclin D1 proteins.
Li
Hong-Liang
HL
Department of Pharmacology, Pharmacy College, Ji-nan University, Guangzhou 510632, China.
Zhang
Hai-Wei
HW
Chen
Dan-Dan
DD
Zhong
Ling
L
Ren
Xian-Da
XD
St-Tu
Rui
R
D017209:Apoptosis / Q000187:drug effects*; D001557:Benzenesulfonates / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins; D010080:Oxazoles / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D000096926:Benzenesulfonamides
D001557:Benzenesulfonates; D053148:Caspase 3; D020169:Caspases; D051546:Cyclooxygenase 2; D007527:Isoenzymes; D008565:Membrane Proteins; D010080:Oxazoles; D011451:Prostaglandin-Endoperoxide Synthases; D012333:RNA, Messenger; C110453:4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide; D000096926:Benzenesulfonamides; C496540:PTGS2 protein, human; C505407:CASP3 protein, human