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Aspirin induces apoptosis in oesophageal cancer cells by inhibiting the pathway of NF‐kappaB downstream regulation of cyclooxygenase‐2
Author(s) -
Liu JunFeng,
Jamieson Glyn G.,
Drew Paul A.,
Zhu GuiJun,
Zhang ShaoWei,
Zhu TieNian,
Shan BaoEn,
Wang QiZhang
Publication year - 2005
Publication title -
anz journal of surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.426
H-Index - 70
eISSN - 1445-2197
pISSN - 1445-1433
DOI - 10.1111/j.1445-2197.2005.03596.x
Subject(s) - apoptosis , aspirin , western blot , medicine , cyclooxygenase , cell growth , cancer research , cell culture , flow cytometry , cancer , microbiology and biotechnology , pharmacology , biology , immunology , enzyme , biochemistry , genetics , gene
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. Conclusion: 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.