The effect of celecoxib on tissue factor expression in pancreatic cancer cells.
BACKGROUND
Tissue factor (TF) is overexpressed in many malignant tumours and is linked to the pathogenesis and prognosis of such malignancies. In vitro studies have proved that reduced expression of TF has inhibitory effect on the angiogenesis and cell proliferation of the malignant tumour. Therefore, TF suppression has been raised as a possible treatment for malignant tumours. Here we investigated the effect of celecoxib on TF expression induced by tumour necrosis factor alpha (TNFalpha) in PANC-1 cells and a possible molecular mechanism underlying the celecoxib effect.


METHODS
Various doses of celecoxib solution were added to standard cell numbers of PANC-1 cells mixed with equal dose of TNFalpha for 6 hours. The expression of tissue factor was detected quantitatively by Western blot, whilst the activation of nuclear factor kappaB was tested by electromobility shift assay.


RESULTS
As the doses of celecoxib increased, the tissue factor expression was decreased in PANC-1 cells and so was the activation of nuclear factor kappaB.


CONCLUSIONS
Celecoxib can downregulate the expression of tissue factor induced by TNFalpha in PANC-1 cells. This antitumour effect of celecoxib can be explained indirectly via its suppressive role in activation of nuclear factor kappaB.
Wang
Hui-yuan
HY
Department of General Surgery, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.
Yang
Yin-mo
YM
Zhuang
Yan
Y
Chen
Huan-nian
HN
Wan
Yuan-lian
YL
Huang
Yan-ting
YT
D000068579:Celecoxib; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013925:Thromboplastin / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D011720:Pyrazoles; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin; D000068579:Celecoxib