In vitro modulation of cisplatin resistance by cytokines.
We have previously demonstrated that treatment of wild-type (wt) T98G malignant glioma cells with Cisplatin (CDDP) led to a resistant phenotype. It has been demonstrated that interleukin 1 (IL-1) potentiates the cytotoxic effect of CDDP and that IL-6 decreases cytotoxicity by inhibition of apoptosis in cancer cells. Here we examined the influence of IL-1 and IL-6 on the sensitivity of resistant and wt T98G cells. Using semi-quantitative PCR reactions in three independent experiments, resistant glioma cells revealed a decreased IL-1alpha (50.3+/-7.2), IL-1beta (56.0+/-4.0) and IL-6 (44. 3+/-18.2) mRNA content compared to wt cells (100%;P<0.05). Resistant and wt cells were positive for the receptors IL-1RI and IL-6R (PCR). To investigate whether IL-1alpha, IL-1beta or IL-6 changes the sensitivity of the resistant and wt cells towards CDDP, cells were incubated up to 7 days with 10(-5) M CDDP and with different concentrations (0, 0.01, 0.1, 1 ng/ml) of cytokine. Sensitivity was tested in a colorimetric assay (MTT). IL-6 did not influence the sensitivity towards CDDP of either wt or resistant cells, while IL-1alpha and IL-1beta enhanced sensitivity of resistant cells to CDDP. These data suggest that autocrine IL-1 production is involved in the mechanisms of resistance in T98G cells.
Poppenborg
H
H
Department of Clinical Pharmacology, University of Leipzig, Leipzig, Germany. popph@srver3.medizin.uni-leipzig.de
Knüpfer
M M
MM
Galla
H J
HJ
Wolff
J E
JE
D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D018076:DNA, Complementary / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D053573:Receptors, Interleukin-1 Type I; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018076:DNA, Complementary; D007375:Interleukin-1; D015850:Interleukin-6; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D019947:Receptors, Interleukin-6; D002945:Cisplatin