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Immunohistochemical detection and quantitation of P-glycoprotein in
multiple drug-resistant human myeloma cells: association with level of drug
resistance and drug accumulation
WS Dalton, TM Grogan, JA Rybski, RJ Scheper, L Richter, J Kailey, HJ Broxterman, HM Pinedo and SE Salmon
Department of Medicine, Arizona Cancer Center, University of Arizona,
Tucson 85724.
Using several multiple drug-resistant human myeloma cell lines as
standards, we developed an immunohistochemical staining technique and means
of quantitating P-glycoprotein in individual myeloma cells. The level of
staining intensity for P-glycoprotein in individual myeloma cells was
quantitated by measuring the average optical density of each cell with a
microscopic computerized cell analysis system. Using this system, we
observed that the level of P-glycoprotein for individual cells within a
cell population of known drug sensitivity was very homogeneous (coefficient
of variation less than or equal to 13%). Analysis of cell lines with
gradually increasing levels of multidrug resistance (8226/S, 8226/Dox6 and
8226/Dox40) demonstrated a close association between the level of
resistance to doxorubicin, defined by the mean lethal dose (D0) and the
amount of P-glycoprotein on individual cells determined by the optical
density (r = 0.82, P less than 0.0005). Intracellular doxorubicin (DOX)
accumulation in the individual cell lines was inversely related to the
level of drug resistance expressed as D0. P-glycoprotein was also detected
in the marrow-derived myeloma cells of patients with drug refractory
disease using immunohistochemical staining. The amount of P-glycoprotein in
the cells of one patient was directly compared to the amount found in the
simultaneously stained standard cell lines (8226/Dox6 and 8226/Dox40) by
comparing the optical densities for individual cells. Using this
immunohistochemical technique to detect and quantitate P-glycoprotein in
patient myeloma cells and comparing it to standard multidrug resistant
myeloma cell lines may be of value in determining the contribution of
P-glycoprotein to clinical drug resistance in patients with multiple
myeloma.
Volume 73,
Issue 3,
pp. 747-752,
02/15/1989
Copyright © 1989 by The American Society of Hematology
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