Aspirin induces apoptosis in oesophageal cancer cells by inhibiting the pathway of NF-kappaB downstream regulation of cyclooxygenase-2.
BACKGROUND
Aspirin has potential in the prevention or treatment of oesophageal cancer, the seventh most common cancer in the world, but its mechanism of action is still not certain.


METHODS
The oesophageal squamous cell carcinoma cell line TE-13 was cultured with aspirin at different concentrations or for different times. Proliferation and apoptosis were measured by MTT reduction and flow cytometry. Expression of COX-2 mRNA was measured by RT-PCR and COX-2 protein levels with Western blot analysis. Nuclear NF-kappaB and cytoplasmic IkappaB protein levels were determined by electrophoretic mobility shift assay and Western blot, respectively.


RESULTS
Aspirin significantly inhibited cell proliferation and induced apoptosis at concentrations of 1, 4, 8 mmol/L. Aspirin dose-dependently decreased the levels of COX-2 mRNA, COX-2 protein and nuclear NF-kappaB protein and increased the cytoplasmic IkappaB protein.


CONCLUSIONS
We conclude that aspirin inhibits the proliferation of, and induced apoptosis in, the cultured TE-13 SCC cell line. These changes correlate with a reduction in COX-2 mRNA and protein expression, prostaglandin synthesis, an inhibition of NF-kappaB nuclear translocation, and an increase in cytoplasmic IkappaB. These results support the further investigation of the cyclooxygenase pathway in investigating the potential of aspirin and similar drugs in cancer prevention and therapy.
Liu
Jun-Feng
JF
Department of Thoracic Surgery, Fourth Hospital, Hebei Medical University, Shijiazhuang, China. liujf@heinfo.net
Jamieson
Glyn G
GG
Drew
Paul A
PA
Zhu
Gui-Jun
GJ
Zhang
Shao-Wei
SW
Zhu
Tie-Nian
TN
Shan
Bao-En
BE
Wang
Qi-Zhang
QZ
D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000378:metabolism*; D003593:Cytoplasm / Q000737:chemistry; D004938:Esophageal Neoplasms / Q000473:pathology*; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis
D008565:Membrane Proteins; D016328:NF-kappa B; D011453:Prostaglandins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D001241:Aspirin