Table 1.

The reversal effect of sildenafil and verapamil on ABCB1-mediated resistancea

CompoundsIC50 ± SDb, μmol/L
KB-3-1KB-C2KB-V1
Colchicine0.0057 ± 0.0015 (1.0)c4.292 ± 1.493 (747.5)0.240 ± 0.035 (41.8)
 +Sildenafil (2.5 μmol/L)0.0062 ± 0.0013 (1.1)0.721 ± 0.236 (125.5)0.059 ± 0.035 (10.3)
 +Sildenafil (5 μmol/L)0.0058 ± 0.0021 (1.0)0.163 ± 0.031 (28.4)0.052 ± 0.022 (9.1)
 +Sildenafil (10 μmol/L)0.0051 ± 0.00148 (0.9)0.060 ± 0.004 (10.5)0.044 ± 0.024 (7.6)
 +Verapamil (2.5 μmol/L)0.0054 ± 0.0016 (0.9)0.264 ± 0.132 (46.0)0.168 ± 0.036 (29.2)
 +Verapamil (5 μmol/L)0.0047 ± 0.0021 (0.8)0.101 ± 0.026 (17.6)0.081 ± 0.037 (14.1)
 +Verapamil (10 μmol/L)0.0032 ± 0.0001 (0.6)0.055 ± 0.009 (9.6)0.055 ± 0.038 (9.6)
Vinblastine0.0452 ± 0.0010 (1.0)c0.464 ± 0.234 (10.3)5.427 ± 3.362 (120.1)
 +Sildenafil (2.5 μmol/L)0.0445 ± 0.0114 (1.0)0.139 ± 0.086 (3.1)0.295 ± 0.211 (6.5)
 +Sildenafil (5 μmol/L)0.0443 ± 0.0076 (1.0)0.092 ± 0.085 (2.0)0.131 ± 0.091 (2.9)
 +Sildenafil (10 μmol/L)0.0437 ± 0.0173 (1.0)0.036 ± 0.016 (0.8)0.084 ± 0.049 (1.9)
 +Verapamil (2.5 μmol/L)0.0400 ± 0.0148 (0.9)0.123 ± 0.109 (2.7)0.238 ± 0.085 (5.3)
 +Verapamil (5 μmol/L)0.0250 ± 0.0038 (0.6)0.056 ± 0.035 (1.2)0.107 ± 0.015 (2.4)
 +Verapamil (10 μmol/L)0.0222 ± 0.0002 (0.5)0.038 ± 0.021 (0.8)0.057 ± 0.013 (1.3)
Paclitaxel0.0056 ± 0.0006 (1.0)c4.380 ± 0.802 (788.5)5.997 ± 1.952 (1,079.6)
 +Sildenafil (2.5 μmol/L)0.0059 ± 0.0014 (1.1)0.056 ± 0.027 (10.0)0.293 ± 0.337 (52.7)
 +Sildenafil (5 μmol/L)0.0057 ± 0.0010 (1.0)0.024 ± 0.016 (4.4)0.144 ± 0.171 (25.8)
 +Sildenafil (10 μmol/L)0.0056 ± 0.0021 (1.0)0.013 ± 0.007 (2.4)0.071 ± 0.040 (12.8)
 +Verapamil (2.5 μmol/L)0.0048 ± 0.0021 (0.9)0.049 ± 0.039 (8.9)0.237 ± 0.308 (42.7)
 +Verapamil (5 μmol/L)0.0042 ± 0.0011 (0.7)0.012 ± 0.003 (2.1)0.055 ± 0.044 (9.9)
 +Verapamil (10 μmol/L)0.0034 ± 0.0007 (0.6)0.009 ± 0.004 (1.7)0.042 ± 0.017 (7.5)
Cisplatin1.745 ± 0.161 (1.0)c1.726 ± 0.083 (1.0)1.756 ± 0.178 (1.0)
 +Sildenafil (2.5 μmol/L)1.637 ± 0.088 (0.9)1.884 ± 0.320 (1.1)1.835 ± 0.071 (1.1)
 +Sildenafil (5 μmol/L)1.601 ± 0.030 (0.9)1.838 ± 0.206 (1.1)1.865 ± 0.006 (1.1)
 +Sildenafil (10 μmol/L)1.628 ± 0.157 (0.9)1.651 ± 0.104 (0.9)1.811 ± 0.081 (1.0)
 +Verapamil (2.5 μmol/L)1.729 ± 0.231 (1.0)1.790 ± 0.250 (1.0)1.784 ± 0.165 (1.0)
 +Verapamil (5 μmol/L)1.623 ± 0.001 (0.9)1.762 ± 0.142 (1.0)1.747 ± 0.056 (1.0)
 +Verapamil (10 μmol/L)1.457 ± 0.007 (0.8)1.738 ± 0.042 (1.0)1.797 ± 0.106 (1.0)
  • 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 colchicines, vinblastine, paclitaxel, and cisplatin of KB-3-1 cells was divided by IC50 value for colchicines, vinblastine, paclitaxel, and cisplatin of KB-3-1, KB-C2, and KB-V1 cells in the absence or presence of sildenafil and verapamil.