Toxoplasma infection and cell free extract of the parasites are able to reverse multidrug resistance of mouse lymphoma and human gastric cancer cells in vitro.
A large number of compounds are known to reduce the ATP-dependent efflux pump activity of multidrug resistant (mdr) tumor cells. Here we report that an infection of cancer cells with T. gondii reduced the multidrug resistance of the tumour cells against cytostatic drugs. Two mouse lymphoma cell lines (Mdr L 5718 and Par 5718) were infected with Toxoplasma gondii in vitro and the reduction of efflux pump activity of the cells was measured. The drug accumulation (Rhodamin-123) was increased in the infected mdr cell lines compared with non- infected mdr-cells, and no effect was shown after infection of the parental cell line. The same effect was also achieved by incubation of Mdr-tumor cells with cell lysate of Toxoplasma gondii. Mdr-1-gene expression was reduced in the infected cell lines 48 hours after infection. Co-cultivation of Toxoplasma gondii with mdr cell lines separated by a microfilter from tumor cells was performed, but this cocultivation did not change the mdr efflux activity. The effect of Toxoplasma gondii infection on the efflux pump activity and mdr-1 gene expression was also examined in the human gastric cancer cells. A sensitization of resistant gastric cancer cells was also achieved by parasite infection. This phenomenon is an evidence that a reduction of resistance in tumor cells can be achieved by a natural parasite infection. It is as yet unclear whether an active infection or another substance of T. gondii is responsible for this phenomenon.
Varga
A
A
Humboldt University Berlin, Department of Molecular Parasitology, Germany. Varginca@hotmail.com
Sokolowska-Kohler
W
W
Presber
W
W
Von Baehr
V
V
Von Baehr
R
R
Lucius
R
R
Volk
D
D
Nacsa
J
J
Hever
A
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000818:Animals; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000469:parasitology; D014122:Toxoplasma / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014617:Vacuoles / Q000502:physiology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1