Modulation of interferon-γ effect by other drug may enhance its tumor specific activity. The apoptosis inducing effect of interferon-γ and its modulation by cyclosporin-A or tacrolimus (FK-506) were investigated in in vitro and ex vivo experiments. We found that a combination of cyclosporin-A (CsA) and recombinant interferon-gamma (rIFN-γ) induced significant apoptosis in all four types of human gastric carcinoma cells tested but not in normal cells such as human peripheral blood mononuclear cells (PBMCs), human omentura-derived mesothelial cells, or human umbilical vein endothelial cells (HUVECs) in vitro. Apoptosis was also induced by a combination of rIFN-γ with FK-506 but not with rapamycin. Next, the apoptosis-inducing effect of endogenous IFN-γ combined with cyclosporin-A was examined using clinical staples. A streptococcal preparation, 0K-432, was administered intraperitoneally for the management of 12 gastric cancer patients with malignant ascites. None of the gascitic fluids obtained before the 0K-432 injection showed detectable IFN-γ level. The 0K-432 injection induced a detectable IFN-γ production ranging from 6 to 89pg/mL in ascitic fiuids from 9 out of the 12 patients. A combination of CsA with ascitic fluids collected after but not before 0K-432 injection induced significant apoptosis in MK-1 cells, a gastric carcinoma cell line. A positive correlation was found between the IFN-γ level and CsA-induced apoptosis. The CsA-induced apoptosis was also blocked by a specific antibody against human IFN-γ. These results indicated that both recombinant and endogenous IFN-γ can induce potent tumor-apoptosis when combined with CsA.
|Number of pages||11|
|Issue number||5 B|
|Publication status||Published - Dec 27 2000|
All Science Journal Classification (ASJC) codes
- Cancer Research