Table 2.

The reversal effect of sildenafil and FTC on ABCG2-mediated resistance in drug-selected cell linesa

CompoundsIC50 ± SDb, μmol/L
S1S1/FLV5000S1-M1-80MCF-7MCF-7/Flv1000MCF-7/ADVP3000
Flavopiridol0.0961 ± 0.0096 (1.0)c6.2046 ± 0.4631 (64.9)0.6992 ± 0.0470 (7.3)0.3443 ± 0.0021 (1.0)c6.8556 ± 0.4794 (19.9)3.9005 ± 0.4139 (11.3)
 +Sildenafil (10 μmol/L)0.0854 ± 0.0291 (0.9)5.4169 ± 0.1866 (56.4)0.1310 ± 0.0192 (1.4)0.3445 ± 0.0342 (1.0)3.3609 ± 0.2038 (9.8)2.0516 ± 0.2546 (6.0)
 +Sildenafil (50 μmol/L)0.0767 ± 0.0292 (0.8)5.1281 ± 0.3575 (53.4)0.0951 ± 0.0351 (1.0)0.3605 ± 0.0445 (1.0)0.4531 ± 0.0151 (1.3)0.5682 ± 0.0321 (1.7)
 +FTC (2.5 μmol/L)0.1239 ± 0.0388 (1.3)5.6540 ± 0.1843 (58.8)0.0948 ± 0.0148 (1.0)0.3441 ± 0.0148 (1.0)0.2777 ± 0.0197 (0.8)0.4166 ± 0.0147 (1.2)
Mitoxantrone0.3796 ± 0.0416 (1.0)c1.1218 ± 0.1437 (3.0)223.60 ± 8.60 (559.3)7.6649 ± 0.1934 (1.0)c511.35 ± 16.71 (66.7)279.25 ± 6.03 (36.4)
 +Sildenafil (10 μmol/L)0.1917 ± 0.0006 (0.5)0.4212 ± 0.1297 (1.1)113.65 ± 12.80 (284.3)2.6792 ± 0.0243 (0.3)127.21 ± 2.62 (16.6)96.77 ± 3.01 (12.6)
 +Sildenafil (50 μmol/L)0.1085 ± 0.0344 (0.3)0.3469 ± 0.0330 (0.9)32.95 ± 2.33 (82.4)1.3434 ± 0.0843 (0.2)36.93 ± 2.12 (4.8)24.39 ± 3.66 (3.2)
 +FTC (2.5 μmol/L)0.3119 ± 0.0310 (0.8)0.9986 ± 0.0218 (2.6)3.55 ± 1.91 (8.9)1.4795 ± 0.2029 (0.2)18.45 ± 1.63 (2.4)13.82 ± 0.67 (1.8)
SN-380.2449 ± 0.0170 (1.0)c0.3442 ± 0.0874 (1.4)3.5533 ± 1.3962 (14.4)1.2218 ± 0.2626 (1.0)c22.827 ± 2.001 (18.7)14.301 ± 1.617 (11.3)
 +Sildenafil (10 μmol/L)0.2488 ± 0.0598 (1.0)0.1647 ± 0.0063 (0.7)1.4886 ± 0.5598 (6.0)0.6009 ± 0.0071 (0.5)10.639 ± 1.537 (8.7)3.861 ± 0.173 (3.2)
 +Sildenafil (50 μmol/L)0.2070 ± 0.0244 (0.8)0.1584 ± 0.0151 (0.6)0.4924 ± 0.0281 (2.0)0.3137 ± 0.0346 (0.3)4.214 ± 0.277 (3.4)1.784 ± 0.086 (1.5)
 +FTC (2.5 μmol/L)0.2808 ± 0.0280 (1.1)0.2933 ± 0.0265 (1.2)0.1014 ± 0.0310 (0.4)0.2993 ± 0.0272 (0.2)2.580 ± 0.132 (2.1)0.198 ± 0.049 (0.2)
Cisplatin14.70 ± 2.23 (1.0)c53.45 ± 5.80 (3.6)18.00 ± 2.59 (1.2)34.41 ± 1.76 (1.0)c35.12 ± 1.86 (1.0)31.12 ± 3.20 (0.9)
 +Sildenafil (10 μmol/L)15.39 ± 2.94 (1.0)56.27 ± 1.93 (3.8)20.08 ± 1.43 (1.4)34.76 ± 0.80 (1.0)34.43 ± 1.32 (1.0)30.72 ± 3.79 (0.9)
 +Sildenafil (50 μmol/L)15.90 ± 3.35 (1.1)56.88 ± 4.19 (3.9)20.64 ± 2.24 (1.4)32.27 ± 1.70 (1.0)34.47 ± 5.58 (1.0)28.01 ± 4.65 (0.8)
 +FTC (2.5 μmol/L)13.27 ± 0.52 (0.9)47.35 ± 4.48 (3.2)15.30 ± 1.38 (1.0)33.24 ± 1.41 (1.0)35.02 ± 1.04 (1.0)31.13 ± 0.33 (0.9)
  • aCell survival was determined by MTT assay as described in the “Materials and Methods” section.

  • bData are means ± SD of at least 3 independent experiments performed in triplicate.

  • cFold-resistance was the value of that IC50 value for flavopiridol, mitoxantrone, SN-38, and cisplatin of S1 or MCF-7 cells was divided by IC50 value for flavopiridol, mitoxantrone, SN-38, and cisplatin of S1, S1/FLV5000, and S1-M1-80 cells or MCF-7, MCF-7/Flv1000, and MCF-7/ADVP3000 in the absence or presence of sildenafil and FTC.