A combination of cyclosporin-A (CsA) and interferon-gamma (INF-γ) iduces apoptosis in human gastric carcinoma cells

T. Morisaki, H. Matsunaga, K. Beppu, E. Ihara, K. Hirano, H. Kanaide, M. Mori, M. Katano

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)3363-3373
Number of pages11
JournalAnticancer research
Volume20
Issue number5 B
Publication statusPublished - Dec 27 2000

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Cyclosporine
Interferon-gamma
Stomach
Apoptosis
Carcinoma
Tacrolimus
Interferons
Injections
Ascitic Fluid
Human Umbilical Vein Endothelial Cells
Sirolimus
Ascites
Stomach Neoplasms
Blood Cells
Neoplasms
Cell Line
Antibodies
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Morisaki, T., Matsunaga, H., Beppu, K., Ihara, E., Hirano, K., Kanaide, H., ... Katano, M. (2000). A combination of cyclosporin-A (CsA) and interferon-gamma (INF-γ) iduces apoptosis in human gastric carcinoma cells. Anticancer research, 20(5 B), 3363-3373.

A combination of cyclosporin-A (CsA) and interferon-gamma (INF-γ) iduces apoptosis in human gastric carcinoma cells. / Morisaki, T.; Matsunaga, H.; Beppu, K.; Ihara, E.; Hirano, K.; Kanaide, H.; Mori, M.; Katano, M.

In: Anticancer research, Vol. 20, No. 5 B, 27.12.2000, p. 3363-3373.

Research output: Contribution to journalArticle

Morisaki, T, Matsunaga, H, Beppu, K, Ihara, E, Hirano, K, Kanaide, H, Mori, M & Katano, M 2000, 'A combination of cyclosporin-A (CsA) and interferon-gamma (INF-γ) iduces apoptosis in human gastric carcinoma cells', Anticancer research, vol. 20, no. 5 B, pp. 3363-3373.
Morisaki, T. ; Matsunaga, H. ; Beppu, K. ; Ihara, E. ; Hirano, K. ; Kanaide, H. ; Mori, M. ; Katano, M. / A combination of cyclosporin-A (CsA) and interferon-gamma (INF-γ) iduces apoptosis in human gastric carcinoma cells. In: Anticancer research. 2000 ; Vol. 20, No. 5 B. pp. 3363-3373.
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