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Characterization of an etoposide-resistant human small-cell lung cancer cell line

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We established an etoposide (VP-16)-resistant human small-cell lung cancer cell line (H69/VP) by stepwise exposure to VP-16. The resistance of H69/VP to VP-16 was 9.4-fold that of the parent cell line (H69/P). H69/VP showed cross-resistance to Adriamycin (ADM), (4S)-4,11-diethyl-4-hydroxy-9-[(4-piperidinopiperidino) carbonyloxy]-1H-pyrano[3′,4′:6,7]indolizino [1,2-b]quinoline-3,14(4H,12H)-dionehydrochloride trihydrate (CPT-11), teniposide (VM-26), vindesine (VDS) and vincristine (VCR). The amount of DNA topoisomerase II (topo.II) was nearly the same in H69/P and H69/VP cells. The catalytic activity of topo.II in H69/VP cells was lower than that in the H69/P line. Accumulation of [3H]-VP-16 in H69/VP was 6.1 – 7.5 times lower than that in H69/P. According to Northern blot analysis, themdr-1 mRNA level in H69/VP was markedly higher than that in H69/P. These findings suggest that H69/VP has a typical multidrug resistance (MDR) phenotype and that alteration of the drug accumulation mediated by P-glycoprotein may play an important role in resistance to VP-16. Reduced topo.II activity may also be associated with VP-16 resistance.

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(4S)-4,11-diethyl-4-hydroxy-9-[(4-piperidinopiperidino)carbonyloxy]-1H-pyrano[3′,4′:6,7]indolizino[1, 2-b]quinoline-3,14(4H,12H)-dionehydrochloride trihydrate








multidrug resistance


DNA topoisomerase II




l-phenylalanine mustard




kinetoplast DNA


phosphatebuffered saline


sodium dodecyl sulfate


ethylendiaminetetraacetic acid


DNA topoisomerase I


Chinese hamster ovary


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Minato, K., Kanzawa, F., Nishio, K. et al. Characterization of an etoposide-resistant human small-cell lung cancer cell line. Cancer Chemother Pharmacol 26, 313–317 (1990).

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