Influence of zymosan (a non-specific macrophage stimulator) and of indomethacin on liver tumours--an experimental study in rats.

Abstract

Zymosan--a non-specific macrophage-stimulating agent--reduces tumour take in the liver. The mechanism for this effect is not clear, but it may be mediated via the Kupffer cells and prostaglandins. On the other hand, the Prostaglandin-synthesis inhibitor, indomethacin, inhibits tumour growth. Pretreatment with zymosan (3 mg 100 g-1) for 3 days of two different strains of rats, inoculated in the liver with a hepatoma or an adenocarcinoma cell suspension respectively, reduced tumour take and also initial tumour growth. The effect on tumour take and initial growth was inhibited by concomitant administration of indomethacin (0.2 mg 100 g-1). When zymosan was administered after tumour cell inoculation the growth rate of the hepatoma was retarded, but this effect was not abrogated by indomethacin. Pretreatment with indomethacin had no significant effect on tumour take or initial growth. When given after the tumour was established in the liver, indomethacin reduced the growth rate of the hepatoma, but not of the adenocarcinoma. These results suggest that there are different mechanisms for the effects of zymosan on tumour take and on growth of an established tumour. In immunoincompetent nude mice the effect on the hepatoma was similar to the effect in the rat. In vitro both tumours were insensitive to zymosan and indomethacin. This study confirms that pretreatment with a non-specific macrophage stimulator (zymosan) diminishes tumour take and growth in the liver, that the effect of zymosan on tumour take in the liver is abrogated by indomethacin and that the zymosan effect on tumour take in the liver is at least partly mediated by the Kupffer cells and prostaglandins.