Induction of growth suppression and modification of gene expression in multi-drug-resistant human glioblastoma multiforme cells by recombinant human fibroblast and immune interferon.
The combination of recombinant human fibroblast (IFN-beta) and immune (IFN-gamma) interferon induces enhanced growth suppression and modifies the antigenic phenotype in parental and multi-drug-resistant (MDR) human glioblastoma multiforme (GBM) cells. The present study was conducted to explore the mechanism underlying this cooperative interaction between interferons in inducing growth suppression in MDR-GBM cells. For this analysis we have utilized 2 MDR-GBM cell lines which display a differential sensitivity to growth suppression when exposed to IFN-beta or IFN-gamma. GBM-18-B3 (MDR) cells are more sensitive to growth inhibition by IFN-gamma than by IFN-beta, whereas GBM-18-A3 (MDR) cells are inhibited to a greater degree by IFN-beta than by IFN-gamma. In both cell types, however, growth is suppressed to a greater degree by the combination of interferons than by equivalent concentrations of either type of interferon used alone. Growth suppression induced by the interferons, alone or in combination, was not associated with comparable changes in the steady-state level of MDRI mRNA. In addition, the anti-proliferative effect of interferon was similar in GBM-18 (MDR) cells grown in the presence or absence of colchicine. GBM-18-A3 and GBM-18-B3 cells differed in their de novo and interferon-inducible expression levels of IFN-beta-responsive genes, isg-15 and isg-54. In contrast, both cell types responded in a similar manner with respect to expression of the IFN-gamma-responsive gene, HLA Class II (HLA-DR beta), and HLA Class I, fibronectin and ICAM-I. No further increase in expression of any of the genes was observed which was unique to the combination of interferons.
Moulton
T A
TA
Division of Hematology/Oncology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Jiang
H
H
Guarini
L
L
Fetell
M R
MR
Fisher
P B
PB
D002455:Cell Division / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D016899:Interferon-beta; D007371:Interferon-gamma; D003078:Colchicine