Anti-Fas antibody-induced apoptosis and its signal transduction in human gastric carcinoma cell lines.
The Fas-Fas ligand system is one of the factors involved in cell death signaling. Aberrations in the signaling pathways leading to Fas-mediated apoptosis in tumor cells have been reported in a variety of human malignant tumors. However, the Fas-mediated apoptotic pathway has not been sufficiently elucidated in human gastric carcinomas. We examined the apoptotic pathway induced by anti-Fas antibody using seven human gastric carcinoma cell lines. Apoptosis was induced in a delayed fashion and the apoptotic indices (AI) after 48 h were approximately 30-40% in MKN-45 and KATO-III cells, which both showed cleavage of the Bid protein and release of Cytochrome c from the mitochondria. Our data also demonstrated no significant relationship between the expressions of various apoptosis-related proteins and the sensitivity or resistance to anti-Fas antibody-induced apoptosis, as far as we examined. Furthermore, the apoptosis signal was inhibited by treatment with Caspase-9 and -3 inhibitors in MKN-45 and KATO-III. These findings suggest that anti-Fas antibody induced apoptosis through the type II signaling pathway in the human gastric carcinoma cell lines, MKN-45 and KATO-III.
Adachi
Keiko
K
Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.
Osaki
Mitsuhiko
M
Kase
Satoru
S
Takeda
Ami
A
Ito
Hisao
H
D017209:Apoptosis; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D045304:Cytochromes c / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D019014:fas Receptor / Q000737:chemistry / Q000276:immunology*
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D019014:fas Receptor; D045304:Cytochromes c; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases