Synergistic antitumor effects of human interferon-beta and interferon-gamma on human gastric adenocarcinoma cells.
The combined effects of different classes of interferon (IFN) on human gastric adenocarcinoma cell line HPE-GAC-2 (GAC-2) were investigated in vitro. Synergistic effects of IFN-beta and -gamma, causing cell death, were observed in a dose-dependent manner. IFN-gamma modulated the sensitivity of GAC-2 cells to the cytocidal effect of IFN-gamma. The modulatory effect was independent of the cytostatic or cytocidal activity of IFN-beta since brief contact with IFN-beta did not influence the growth kinetics of the cells and was effective in modulate the cellular sensitivity to IFN-gamma. A brief pretreatment of the cells with IFN-alpha or-beta resulted in a variable level of modulation, whereas coculture of the cells with IFN-beta or -alpha and IFN-gamma had a similar cytotoxic effect indicating a different level of activity induced by IFN-alpha and -beta with the common type I receptor. These results suggest that IFN-beta-induced modulation was receptor-mediated. Phase contrast microscopy showed evidence of apoptotic cell death induced by one or more IFN agents. The morphological changes included chromatin condensation and nuclear fragmentation which were apparent at as early as 6 hr of culture with a high concentration of IFN(s). Our results indicate that IFN-beta and IFN-alpha enhance the in vitro apoptotic effects of IFN-gamma against GAC-2 tumor cells.
Nagao
S
S
Department of Pathology, Shimane Medical University.
Nakano
A
A
Moritake
K
K
Morikawa
S
S
Harada
T
T
D000230:Adenocarcinoma / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016899:Interferon-beta; D007371:Interferon-gamma