Antitumour activity of orally administered<i>lactobacillus casei:</i>significance of its dose in the inhibition of a fibrosarcoma in mice

Abstract

The effect of previous oral administration of Lactobacillus casei used as immunomodulator on the inhibition of a fibrosarcoma (a non‐intestinal tumour) was studied. BALB/c mice were fed with different doses of L. casei (2.4, 6 and 8.4 × 109 bacteria). At the end of each treatment, 5 × 105 tumour cells from a methylcholanthrene‐induced fibrosarcoma were subcutaneously inoculated, tumour progression being studied for 35 days. Results showed that feeding with a 2.4 × 109 dose of L. casei before inoculation of the tumour cells caused a 41% suppression in tumour growth. In the case of those animals fed with the same dose in which there was no inhibition of tumour growth, an increase of 55 days in survival time was observed as against a control survival period of only 35 days. The other doses assayed proved unable to check tumour growth; on the contrary, they favoured it. In order to study the reason for the different behaviour of the various doses of L. casei tested as regards tumour inhibition, we carried out (a) measurements of alkaline phosphatase levels to determine inflammatory response, (b) haematological studies and (c) in vitro phagocytosis assays to measure the activation levels of peritoneal macrophages. All these assays were effected both after the various L. casei feeding periods and on the 6th and 12th days after tumour cell inoculation. In all cases, phagocytosis values were similar to those of the controls. The inflammatory response increased on the 5th and 7th days after feeding with L. casei, with slight haematological modifications being observed for these periods, while treatment with a 2.4 × 109 cell dose of the microorganism (a 2‐day previous feeding period) caused no haematological alterations. Although we still lack knowledge of the exact mechanism(s) through which L. casei is capable of inhibiting tumour growth, we were able to demonstrate that the above microorganism, orally administered, can exert an antitumoural effect in tumours histologically distant from the immunomodulator penetration route and that this inhibition is closely related to the administered dose.