Varga A, Sokolowska-Kohler W, Presber W, Von Baehr V, Von Baehr R, Lucius R, Volk D, Nacsa J, Hever A
Humboldt University Berlin, Department of Molecular Parasitology, Germany.
Anticancer Res. 1999 Mar-Apr;19(2A):1317-24.
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.
已知大量化合物可降低多药耐药（mdr）肿瘤细胞的ATP依赖性外排泵活性。在此我们报告，用刚地弓形虫感染癌细胞可降低肿瘤细胞对细胞毒性药物的多药耐药性。将两种小鼠淋巴瘤细胞系（Mdr L 5718和Par 5718）在体外感染刚地弓形虫，并检测细胞外排泵活性的降低情况。与未感染的mdr细胞相比，感染的mdr细胞系中药物蓄积（罗丹明-123）增加，而亲代细胞系感染后未显示出效果。用刚地弓形虫细胞裂解物孵育Mdr肿瘤细胞也能达到同样的效果。感染后48小时，感染的细胞系中Mdr-1基因表达降低。进行了刚地弓形虫与通过微滤器与肿瘤细胞分离的mdr细胞系的共培养，但这种共培养并未改变mdr外排活性。还在人胃癌细胞中检测了刚地弓形虫感染对外排泵活性和mdr-1基因表达的影响。寄生虫感染也使耐药胃癌细胞致敏。这一现象证明，通过自然寄生虫感染可降低肿瘤细胞的耐药性。目前尚不清楚是活跃感染还是刚地弓形虫的其他物质导致了这一现象。
