Table 3.

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

CompoundsIC50 ± SDb, μmol/L
HEK293/pcDNA3HEK/ABCG2-G2HEK/ABCG2-R5HEK/ABCG2-T7
Flavopiridol0.1640 ± 0.0171 (1.0)c0.3976 ± 0.0910 (2.4)0.2821 ± 0.0148 (1.7)0.7578 ± 0.0423 (4.6)
 +Sildenafil (10 μmol/L)0.1493 ± 0.0059 (0.9)0.1216 ± 0.0112 (0.7)0.1670 ± 0.0107 (1.0)0.2256 ± 0.0108 (1.4)
 +Sildenafil (50 μmol/L)0.1599 ± 0.0180 (1.0)0.1122 ± 0.0117 (0.7)0.1466 ± 0.0030 (0.9)0.1916 ± 0.0316 (1.2)
 +FTC (2.5 μmol/L)0.1276 ± 0.0033 (0.8)0.0988 ± 0.0386 (0.6)0.1643 ± 0.0236 (1.0)0.1643 ± 0.0296 (1.0)
Mitoxantrone0.0356 ± 0.0030 (1.0)c1.1042 ± 0.6023 (31.0)0.4574 ± 0.3924 (12.8)0.8424 ± 0.185 8 (23.7)
 +Sildenafil (10 μmol/L)0.0115 ± 0.0007 (0.3)0.0875 ± 0.0045 (2.5)0.1142 ± 0.0004 (3.2)0.1168 ± 0.0118 (3.3)
 +Sildenafil (50 μmol/L)0.0057 ± 0.0006 (0.2)0.0429 ± 0.0061 (1.2)0.0784 ± 0.0207 (2.2)0.0418 ± 0.0020 (1.2)
 +FTC (2.5 μmol/L)0.0315 ± 0.0092 (0.9)0.0696 ± 0.0054 (2.0)0.0420 ± 0.0156 (1.2)0.0919 ± 0.0208 (2.6)
SN-380.0058 ± 0.0002 (1.0)c0.2042 ± 0.1362 (2.3)0.1282 ± 0.0882 (22.1)0.1171 ± 0.0704 (20.2)
 +Sildenafil (10 μmol/L)0.0034 ± 0.0010 (0.6)0.0101 ± 0.0021 (1.7)0.0175 ± 0.0018 (3.0)0.0488 ± 0.0186 (8.4)
 +Sildenafil (50 μmol/L)0.0019 ± 0.0003 (0.3)0.0044 ± 0.0100 (0.8)0.0063 ± 0.0029 (1.1)0.0139 ± 0.0025 (2.4)
 +FTC (2.5 μmol/L)0.0036 ± 0.0092 (0.8)0.0050 ± 0.0009 (1.9)0.0081 ± 0.0051 (1.4)0.0082 ± 0.0023 (1.4)
Cisplatin1.6300 ± 0.1697 (1.0)c1.2305 ± 0.0841 (0.8)1.3265 ± 0.2001 (0.8)1.8435 ± 0.0233 (1.1)
 +Sildenafil (10 μmol/L)1.5640 ± 0.0156 (1.0)1.1371 ± 0.1577 (0.7)1.3855 ± 0.0955 (0.9)1.8115 ± 0.0403 (1.1)
 +Sildenafil (50 μmol/L)2.0180 ± 0.4285 (1.2)1.1993 ± 0.1429 (0.7)1.9820 ± 0.0438 (1.2)1.9680 ± 0.0665 (1.2)
 +FTC (2.5 μmol/L)1.1535 ± 0.0488 (0.7)1.0466 ± 0.028 (0.6)1.3495 ± 0.2072 (0.8)1.9530 ± 0.0834 (1.2)
  • 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 carried out ed in triplicate.

  • cFold-resistance was the value of that IC50 value for flavopiridol, mitoxantrone, SN-38, and cisplatin of HEK293/pcDNA3 cells was divided by IC50 value for flavopiridol, mitoxantrone, SN-38, and cisplatin of HEK293/pcDNA3, HEK293/ABCG2-G2, HEK293/ABCG2-R5, and HEK293/ABCG2-T7 cells in the absence or presence of sildenafil and FTC.