Synergistic effects of CDDP and OK-432-stimulated PBMC-producing cytokine mixture on tumor cell growth: A possible role of apoptosis

The streptococcal preparation, OK-432, is known to induce several antitumor cytokines (cytokine mixture) such as IFN, TNF, and TGIF in human peripheral blood mononuclear cells (PBMC). In this paper, the effect of CDDP and OK-432 induced cytokine mixture on the induction of apoptosis in a human gastric carcinoma cell line, MK-1, was investigated. Apoptosis was determined by morphological features and DNA fragmentation analysis. The cytokine mixture induced apoptosis in MK-1 cells in a dose and time dependent manner. The combination of a subthreshold concentration of CDDP and the cytokine mixture induced both significant growth inhibition and significant DNA fragmentation in MK 1 cells, which indicates that the effects of CDDP and cytokine mixture are synergistic.