Flavone acetic acid antitumour activity against a mouse pancreatic adenocarcinoma is mediated by natural killer cells

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Abstract

Flavone acetic acid (FAA) is one of the most active antitumour agents against mouse solid tumours. A number of reports favour the hypothesis that FAA could behave as a biological response modifier; in fact FAA stimulates natural killer (NK) cells, induces secretion of type I interferon and synergizes with interleukin-2 to increase NK/lymphokine-activated killer (LAK) activity in vivo. However, there is no conclusive evidence that the antitumour activity of FAA is mediated via the modulation of NK/LAK cells. The present study was designed to evaluate whether the reported activation of NK cells is instrumental in FAA antitumour activity. FAA (180 mg/kg, i.v. on days 3, 7 and 11 after tumour implant) was significantly effective in inhibiting the subcutaneous growth of the pancreatic adenocarcinoma PAN/03 in C57/B1 mice. After 132 days the number of tumour-free survivors was 36%, whereas in the control group receiving no treatment, or in the group of mice treated with 10 μg/mouse of α-asialo-GM1 the value was only 0 or 6.7%, respectively. The combination of FAA and α-asialo-GM1 resulted in only 6% tumour-free mice. In parallel experiments, splenocytes and peritoneal cells from C57/Bl mice were tested in a standard cytotoxicity NK assay. While animals treated with FAA showed a significant increase in NK activity, those injected with α-asialo-GM1 had very low levels, and the combined treatment of FAA and α-asialo-GM1 resulted in a lower or similar NK activity compared to that in untreated mice. The fact that the abrogation of the NK-stimulating effect of FAA is accompanied by a lack of anti-tumour activity indicates that, at least in this experimental model, FAA is likely to act via an immunomodulatory mechanism.

Original languageEnglish
Pages (from-to)241-244
Number of pages4
JournalCancer Immunology, Immunotherapy
Volume32
Issue number4
DOIs
Publication statusPublished - Jul 1990

ASJC Scopus subject areas

  • Oncology
  • Immunology
  • Cancer Research

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