Table 1

Cross-resistance profile of Mdr1a/b−/− Mrpl−/− fibroblast lines selected for resistance to mitoxantrone, topotecan, or doxorubicin

The IC50s shown (nm) are the means ± SD of results from three experiments, each performed in quadruplicate. Resistance factors (RF) in parentheses are the ratios of the mean IC50s for the resistant sublines and their sensitive parental lines. Differences in those means were tested with one-tailed (resistant > sensitive) heteroscedastic t tests; they were statistically significant (P < 0.05) except where indicated by “ns” (not significant).
IC50 ± SD, nm (resistance factor)
DrugUnselected parent line MEF3.8Mitoxantrone-selectedM32RFTopotecan-selectedT6400RFUnselected parent line KOT52Doxorubicin-selectedD320RF
Mitoxantrone0.81 ± 0.25142 ± 8(174)53 ± 6(66)1.35 ± 0.15403 ± 42(299)
Bisantrene12.5 ± 3.0215 ± 22(17)110 ± 10(8.8)10.6 ± 2.11,420 ± 770(134)
Doxorubicin6.4 ± 1.056 ± 8(8.7)33 ± 9(5.2)3.4 ± 0.51,180 ± 300(350)
Daunorubicin7.4 ± 1.514.5 ± 0.5(2.0)12.3 ± 1.2(1.7)4.1 ± 0.3318 ± 19(78)
Etoposide53 ± 6593 ± 64(11)307 ± 123(5.8)28 ± 83,970 ± 1,110(142)
Topotecan49 ± 36,400 ± 2,000(132)16,000 ± 5,300(329)183 ± 7428,700 ± 3,100(156)
Vincristine0.38 ± 0.030.64 ± 0.07(1.7)ns0.63 ± 0.23(1.6)ns0.66 ± 0.371.01 ± 0.17(1.5)ns
Paclitaxel4.5 ± 0.38.4 ± 1.9(1.9)9.1 ± 3.0(2.0)ns2.2 ± 0.54.9 ± 0.2(2.2)
Cisplatin1,500 ± 7802,630 ± 250(1.8)ns3,270 ± 570(2.2)2,670 ± 3802,050 ± 560(0.77)ns