RRC ID 1454
著者 Honjo S, Osaki M, Ardyanto TD, Hiramatsu T, Maeta N, Ito H.
タイトル COX-2 inhibitor, NS398, enhances Fas-mediated apoptosis via modulation of the PTEN-Akt pathway in human gastric carcinoma cell lines.
ジャーナル DNA Cell Biol
Abstract A variety of human cancer cells are resistant to Fas ligand and anti-Fas antibody induced apoptosis. Previously, we reported that human gastric carcinoma cell lines were resistant to the anti-Fas antibody, CH-11, without interferon-gamma pretreatment in vitro. Cyclooxygenase (COX)-2 is known to be expressed in many human malignancies, and is correlated with tumor progression and resistance to apoptosis. This study examined whether NS398, a COX-2 inhibitor, inhibited cell proliferation and increased Fas-mediated apoptosis in human gastric carcinoma cell lines. Treatment of NS398 inhibited cell proliferation in MKN-45, which expressed the highest level of COX-2 among seven human gastric carcinoma cell lines, in a dose- and time-dependent manner, in contrast to less prominent effects in KATO-III, which expresses no COX-2. Although the treatment of CH-11 induced apoptosis in both cells, the simultaneous treatment of NS398 and CH-11 remarkably induced apoptosis, as confirmed by Hoechst 33258 staining and the terminal deoxynucleotidyl transferase- mediated dUTP-digoxigenin nick-end labeling (TUNEL) method in MKN-45. Flow cytometric analysis also revealed the increased pre-G1 fraction by the simultaneous treatment. The treatment of NS398 induced upregulation of Bad and PTEN, and downregulation of phosphorylated Akt (Thr308). These findings suggest that COX-2 might inhibit Fas-mediated apoptosis in human gastric carcinoma cell lines, especially MKN-45, by modulating PTEN and Akt.
巻・号 24(3)
ページ 141-7
公開日 2005-3-1
DOI 10.1089/dna.2005.24.141
PMID 15767780
MeSH Antibodies / pharmacology Antineoplastic Agents / pharmacology* Apoptosis / drug effects Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors / pharmacology* Down-Regulation Fas Ligand Protein Flow Cytometry Humans In Situ Nick-End Labeling Membrane Glycoproteins / pharmacology* Membrane Proteins Nitrobenzenes / pharmacology* PTEN Phosphohydrolase Phosphoric Monoester Hydrolases / metabolism* Phosphorylation Prostaglandin-Endoperoxide Synthases / metabolism Protein Serine-Threonine Kinases / metabolism* Proto-Oncogene Proteins / metabolism* Proto-Oncogene Proteins c-akt Signal Transduction / drug effects Stomach Neoplasms / metabolism* Sulfonamides / pharmacology* Tumor Cells, Cultured Tumor Suppressor Proteins / metabolism*
IF 3.314
引用数 20
WOS 分野 GENETICS & HEREDITY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 MKN7(RCB0999) MKN45(RCB1001) MKN74(RCB1002)