PMID: 2499665Apr 1, 1989Paper

Heterogeneous response of human colon cancer cells to the cytostatic and cytotoxic effects of recombinant human cytokines: interferon-alpha, interferon-gamma, tumor necrosis factor, and interleukin-1

Journal of Biological Response Modifiers
K Morikawa, I J Fidler

Abstract

We examined whether different human colorectal carcinomas (HCC) and cells populating a single neoplasm exhibit a heterogeneous response to the cytostatic and cytolytic effects of recombinant human cytokines used clinically for cancer therapy. The effects of interferon-alpha (IFN-alpha) hybrid BBDD, interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), interleukin-1 (IL-1), and the chemotherapeutic drug 5-fluorouracil (used as a positive control for cytostasis) were examined in six recently established HCC cell lines. One cell line was sensitive to the cytostatic and cytotoxic effects of IFN-alpha BBDD, whereas five cell lines were sensitive to IFN-gamma. Tumor cell sensitivity to IFN-alpha BBDD was independent of sensitivity to IFN-gamma. Only one cell line was somewhat sensitive to the cytostatic and cytotoxic effect of TNF, and none was sensitive to IL-1. The heterogeneous response to cytokines by a single neoplasm was demonstrated by analysis of multiple clones. Clonal populations exhibited different levels of susceptibility to cytostatic effects mediated by cytokines. The combination of IFN-gamma with IFN-alpha BBDD or with TNF produced additive or even synergistic cytostasis in HCC lines sensitive to the cytokines but...Continue Reading

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