| Publication number |
CLPUB00485 |
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| Authors |
Kuiper C.M., Broxterman H.J., Baas F., Schuurhuis G.J., Haisma H.J., Scheffer G.L., Lankelma J., Pinedo H.M. |
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| Title |
Drug transport variants without P-glycoprotein overexpression from a human squamous lung cancer cell line after selection with doxorubicin. |
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| Citation |
J. Cell. Pharmacol. 1:35-41(1990) |
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| Abstract |
A series of cell lines with increasing levels of multidrug resistance,
SW-1573/2R50, 2R80, 2R120, 2R160 and 2R250, was derived by selection with
doxorubicin from the human squamous lung cancer cell line SW-1573 in order
to study the expression of P-glycoprotcin during subsequent stages of
resis-tance development. Up to SW-1573/2R120 the cell lines exhibited low
levels of cross-resistance to vincristine, and gramicidin D, but
relatively high levels of cross-resistance to etoposide. Cellular
accumulation of daunorubicin and vincristine was markedly decreased in all
sublines and a small modulation of resistance levels and drug accumulation
by verapamil could be detected. However, no P-glycoprotein could be
detected by Western blotting using C219 and no overexpression of the indr1
gene occurred in these sublines. Cell lines SW-1573/2R160 and SW-1573/2R250
display a large increase in doxorubicin resistance levels coinciding with a
large overexpression of P-glycoprotein (about 3.5 x 10E5 molecules/cell) as
calculated from binding experiments with 125I-labeled MRK-16. These findings
indicate that early steps of pleiotropic resistance to anticancer drugs,
induced by doxorubicin selection, can be mediated by other mechanisms than a
gradual increase in P-glycoprotein expression. This mechanism gives a
relatively high etoposide resistance. As a consequence, low level, drug
transport-dependent resistance might be missed by detection methods using
mdr-1 specific reagents.
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| Cell lines |
CVCL_1720; SW1573 CVCL_WG75; SW1573/2R50 CVCL_WG76; SW1573/2R80 CVCL_WG70; SW1573/2R120 CVCL_WG71; SW1573/2R160 CVCL_WG77; SW1573/2R250 |
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