Toxoplasma infection and cell free extract of the parasites are able to reverse multidrug resistance of mouse lymphoma and human gastric cancer cellsin vitro

A large number of compounds are known to reduce the ATP-dependent efflux pu mp activity of multidrug resistant (mdr) tumor cells. Here we report that a n infection of cancer cells with T. gondii reduced the multidrug resistance of the tumour cells against cytostatic drugs. Two mouse lymphoma cell line s (Mdr L 5718 and Par 5718) were infected with Toxoplasma gondii in vitro a nd the reduction of efflux pump activity of the cells was measured. The dru g accumulation (Rhodamin-123) was increased in the infected mdr cell lines compared with non-infected mdr-cells, and no effect was shown after infecti on of the parental cell line. The same effect was also achieved by incubati on of Mdr-tumor cells with cell lysate of Toxoplasma gondii. Mdr-1-gene exp ression was reduced in the infected cell lines 48 hours after infection. Co cultivation of Toxoplasma gondii with mdr cell lines separated by a microfi lter from tumor cells was performed, but this cocultivation did not change the mdr efflux activity. The effect of Toxoplasma gondii infection on the e fflux pump activity and mdr-1 gene expression was also examined in the huma n gastric cancer cells. A sensitization of resistant gastric cancer cells w as also achieved by parasite infection. This phenomenon is an evidence that a reduction of resistance in tumor cells can be achieved by a natural para site infection. It is as yet unclear whether an active infection or another substance of T. gondii is responsible for this phenomenon.