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Anti-proliferative effect on human pancreatic cancer cells of natural human tumour necrosis factor-beta combined with natural human interferon-alpha or interferon-gamma. 1992

T Watanabe, and S Fuchimoto, and N Matsubara, and H Iwagaki, and K Orita
First Department of Surgery, Okayama University Medical School, Japan.

The anti-proliferative effects of natural cytokines, human tumour necrosis factor-beta, natural human interferon-alpha and natural human interferon-gamma, on three human pancreatic cancer cell lines (PANC-1, MIA PaCa-2 and BxPC-3) were investigated in vitro. The anti-proliferative effect was determined using the dye uptake method and analysed for synergism by the median effect principle. Tumour necrosis factor-beta, as a single agent, had little anti-proliferative effect on any of the three cell lines, whereas interferon-alpha and interferon-gamma exhibited a strong anti-proliferative effect against two cell lines (MIA PaCa-2 and BxPC-3) and one cell line (BxPC-3), respectively. When tumour necrosis factor-beta and interferon-alpha were administered together (ratio 1:1), a synergistic effect was observed against PANC-1 cells. The combination of tumour necrosis factor-beta and interferon-gamma (ratio 10:1) was synergistic against both PANC-1 and MIA PaCa-2 cells. A synergistic anti-proliferative effect of tumour necrosis factor-beta and interferons was, therefore, observed even for cell lines that showed little biological response to each cytokine alone. The data suggest that some future improvement in the treatment of pancreatic cancer may be obtained by using combination cytokine therapy.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008233 Lymphotoxin-alpha A tumor necrosis factor family member that is released by activated LYMPHOCYTES. Soluble lymphotoxin is specific for TUMOR NECROSIS FACTOR RECEPTOR TYPE I; TUMOR NECROSIS FACTOR RECEPTOR TYPE II; and TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY, MEMBER 14. Lymphotoxin-alpha can form a membrane-bound heterodimer with LYMPHOTOXIN-BETA that has specificity for the LYMPHOTOXIN BETA RECEPTOR. TNF Superfamily, Member 1,TNF-beta,Tumor Necrosis Factor Ligand Superfamily Member 1,Tumor Necrosis Factor-beta,Lymphotoxin,Lymphotoxin-alpha3,Soluble Lymphotoxin-alpha,alpha-Lymphotoxin,Lymphotoxin alpha,Lymphotoxin alpha3,Lymphotoxin-alpha, Soluble,Soluble Lymphotoxin alpha,Tumor Necrosis Factor beta,alpha Lymphotoxin
D010190 Pancreatic Neoplasms Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA). Cancer of Pancreas,Pancreatic Cancer,Cancer of the Pancreas,Neoplasms, Pancreatic,Pancreas Cancer,Pancreas Neoplasms,Pancreatic Acinar Carcinoma,Pancreatic Carcinoma,Acinar Carcinoma, Pancreatic,Acinar Carcinomas, Pancreatic,Cancer, Pancreas,Cancer, Pancreatic,Cancers, Pancreas,Cancers, Pancreatic,Carcinoma, Pancreatic,Carcinoma, Pancreatic Acinar,Carcinomas, Pancreatic,Carcinomas, Pancreatic Acinar,Neoplasm, Pancreas,Neoplasm, Pancreatic,Neoplasms, Pancreas,Pancreas Cancers,Pancreas Neoplasm,Pancreatic Acinar Carcinomas,Pancreatic Cancers,Pancreatic Carcinomas,Pancreatic Neoplasm
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016898 Interferon-alpha One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells. In addition to antiviral activity, it activates NATURAL KILLER CELLS and B-LYMPHOCYTES, and down-regulates VASCULAR ENDOTHELIAL GROWTH FACTOR expression through PI-3 KINASE and MAPK KINASES signaling pathways. Interferon Alfa,Interferon, Leukocyte,Interferon, Lymphoblast,alpha-Interferon,IFN-alpha D,IFN-alpha5,Interferon alpha-1,Interferon alpha-17,Interferon alpha-4,Interferon alpha-5,Interferon alpha-7,Interferon alpha-88,Interferon alpha-J,Interferon alpha-T,Interferon alpha4,Interferon alpha5,Interferon, Lymphoblastoid,Interferon, alpha,LeIF I,LeIF J,Leif D,IFN alpha D,IFN alpha5,Interferon alpha,Interferon alpha 1,Interferon alpha 17,Interferon alpha 4,Interferon alpha 5,Interferon alpha 7,Interferon alpha 88,Interferon alpha J,Interferon alpha T,Leukocyte Interferon,Lymphoblast Interferon,Lymphoblastoid Interferon,alpha Interferon
D016899 Interferon-beta One of the type I interferons produced by fibroblasts in response to stimulation by live or inactivated virus or by double-stranded RNA. It is a cytokine with antiviral, antiproliferative, and immunomodulating activity. Interferon, Fibroblast,beta-Interferon,Fiblaferon,Interferon, beta,Interferon, beta-1,Interferon-beta1,beta-1 Interferon,Fibroblast Interferon,Interferon beta,Interferon beta1,Interferon, beta 1,beta 1 Interferon,beta Interferon

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