Journal Article

Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak

Xin Min Zhou, Benjamin Chun Yu Wong, Xiao Ming Fan, Hong Bo Zhang, Marie Chia Mi Lin, Hsiang Fu Kung, Dai Ming Fan and Shiu Kum Lam

in Carcinogenesis

Volume 22, issue 9, pages 1393-1397
Published in print September 2001 | ISSN: 0143-3334
Published online September 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.9.1393
Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak

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Aspirin- and non-steroidal anti-inflammatory drug (NSAID)-induced apoptosis is one of the important mechanisms for their anti-tumour effect in gastric cancer. We aimed at determining the role of bcl-2 family proteins and caspases in the apoptotic process. Gastric cancer cell lines AGS (wild-type p53) and MKN-28 (mutant p53) were used. Cell proliferation was measured by MTT assay. Apoptosis was determined by acridine orange staining. Protein expressions were determined by western blotting. Aspirin and indomethacin inhibited cell proliferation and induced apoptosis in both cells. AGS cells were more sensitive compared with MKN-28 cells. The pro-apoptotic proteins bax and bak were overexpressed after treatment, while the protein level of bcl-2 remained unchanged. Apoptosis was accompanied by an increase in caspase-3 activity and cleavage of caspase-3 and poly(ADP-ribose) polymerase. Inhibition of caspase-3 rescued aspirin-induced apoptosis. Our results suggest that one of the major pathways which mediates the anti-tumour response of aspirin and indomethacin in gastric cancer cells is through up-regulation of bax and bak and activation of caspase-3. Bax and bak are important in the chemoprevention of gastric cancer.

Keywords: NSAIDs, non-steroidal anti-inflammatory drugs; PARP, poly(ADP-ribose) polymerase; TBS-T, 10 mM Tris–HCl buffered saline; pH 7.6, plus 0.05% Tween-20.

Journal Article.  3848 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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