The regulatory effect of the p38 signaling pathway on valdecoxib-induced apoptosis of the Eca109 cell line.
Valdecoxib is a second generation selective COX-2 inhibitor that can induce cell apoptosis in a variety of cell types, but its precise regulatory mechanism is unknown. Apoptosis of Eca109 cells and p38 mRNA expression were investigted. The expression of p-p38MAPK, Fas and FasL proteins were detected by immunohistochemical staining and FCM. Valdecoxib increased the apoptosis rate of Eca109 cells. Fas and FasL protein expression was up-regulated in the valdecoxib groups, while SB203580 partly inhibited the valdecoxib-induced overexpression. Valdecoxib increased p38MAPK expression, while SB203580 inhibited the overexpression of this protein and the apoptosis rate decreased. The expression of Fas, FasL and p38MAPK protein were positively correlated with the apoptotic rate. In conclusion, valdecoxib activates the p38MAPK pathway, thus up-regulating expression of the Fas and FasL proteins, which may be one of the mechanisms through which valdecoxib induces apoptosis.
Liu
Shu-Xia
SX
Department of pathology, Hebei Medical University, Shijiazhuang 050017, People's Republic of China.
Zhang
Yu-Jun
YJ
Guo
Hui-Fang
HF
Hao
Jun
J
Liu
Qing-Juan
QJ
Liu
Jun-Ru
JR
Guo
Jian-Wen
JW
Liu
Jiang-Hui
JH
Zuo
Lian-Fu
LF
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053222:Fas Ligand Protein / Q000032:analysis; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology*; D019014:fas Receptor / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*; D000096926:Benzenesulfonamides
D016861:Cyclooxygenase Inhibitors; D053222:Fas Ligand Protein; D007555:Isoxazoles; D013449:Sulfonamides; D019014:fas Receptor; D048051:p38 Mitogen-Activated Protein Kinases; C505661:FASLG protein, human; C406224:valdecoxib; D000096926:Benzenesulfonamides