Cell Surface P-Glycoprotein Associated with Multidrug Resistance in Mammalian Cell Lines

Abstract

The plasma membranes of hamster, mouse, and human tumor cell lines that display multiple resistance to drugs were examined by gel electrophoresis and immunoblotting. In every case, increased expression of a 170,000-dalton surface antigen was found to be correlated with multidrug resistance. This membrane component is of identical molecular size and shares some immunogenic homology with the previously characterized P-glycoprotein of colchicine-resistant Chinese hamster ovary cells. This finding may have application to cancer therapy.

Increased expression of cyclin E is associated with an increased resistance to doxorubicin in rat fibroblasts

“…One of the major mechanisms of resistance to doxorubicin is due to the acquisition of the so-called multiple drug resistance (MDR) phenotype which, in most of the cases, depends on the expression of a transmembrane 170 kDa glycoprotein, called P-glycoprotein (Kartner et al, 1983). Cells that develop resistance through the MDR mechanism, however, simultaneously develop cross-resistance to several structurally unrelated natural products, including anthracyclines, vinka alkaloids, epipodophyllotoxins, taxanes and actinomycin-D (Kartner et al, 1983).…”

“…Cells that develop resistance through the MDR mechanism, however, simultaneously develop cross-resistance to several structurally unrelated natural products, including anthracyclines, vinka alkaloids, epipodophyllotoxins, taxanes and actinomycin-D (Kartner et al, 1983). Since the Rat-E cells only displayed an increased resistance to doxorubicin, but not to the vinca alkaloid vincristine, nor to paclitaxel, the acquisition of an MDR-phenotype in these cells is unlikely.…”

O6‐methylguanine‐DNA methyltranspherase gene expression in gliomas by means of real‐time quantitative RT‐PCR and clinical response to nitrosoureas

“…Multidrug-resistance genes (MDRs) have been thought to be associated with resistance to vincristine, etoposide, and other drugs. [23][24][25][26] Recently, multidrug resistance-associated proteins (MRPs) have also been considered to be important in resistance to these drugs. 27 Some drug-resistance genes, such as glutathion-S transferase (GST), glutathion, and metallothionein, are thought to be related to the sensitivity to Pt-compounds.…”

Long-term exposure to irinotecan reduces cell migration in glioma cells

“…We were interested in observing whether changes in drug resistance and invasion occurred, in a model glioma cell line (C6), following exposure to topoisomerase I and topoisomerase II inhibition. Initially, we explored whether etoposide (topoisomerase II inhibitor) and irinotecan (topoisomerase I inhibitor) were cytotoxic against the C6 cell line and used a clonogenic assay to determine IC50,70 values (the concentration of drug required to achieve 50 or 70%-maximal inhibition of colony growth; Figure 1 A common mechanism that might be expected to show alteration upon drug selection is the upregulation of ABC transporters of the multidrug resistance family [20]. We saw increased expression of ABCB1/P-glycoprotein in both cell lines compared to a DMSO (vehicle control) selected C6 cell line 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 cell line ( Figure 2B).…”