Table 2. GI50 values for vincristine in the presence of verapamil, Nutlin-3, NDD0005, MI-63 and RG7388 in p53 mutant high MDR-1-expressing SKNBe2C and low MDR-1-expressing SKNAS, and p53 wt high MDR-1-expressing SHSY5Y neuroblastoma cells and the fold potentiation relative to vincristine alone.
|
|
72 h GI50
of vincristine (nM) |
Fold potentiation |
||||
---|---|---|---|---|---|---|---|
Compound | Cell line | 1 μM/0.25 × a | 2 μM/0.5 × a | 5 μM/1 × a | 1 μM/0.25 × a | 2 μM/0.5 × a | 5 μM/1 × a |
SKNBe2C | 4.2±0.6 | 2.2±0.3 | 1.1±0.2 | 10.5 | 19.9 | 38.2 | |
P<0.05 | P<0.05 | P<0.05 | |||||
Verapamil | SKNAS | 1.2±0.1 | 1.1±0.1 | 0.9±0.1 | 1.1 | 1.1 | 1.3 |
P=0.259 | P=0.185 | P=0.121 | |||||
SHSY5Y | 0.5±0.2 | 0.2±0.1 | <0.1 nM | 10.2 | 21.8 | >50 | |
|
|
|
|
|
P<0.001 |
P<0.001 |
P<0.001 |
SKNBe2C | 20.1±6.2 | 3.1±1.5 | 1.0±0.2 | 2.1 | 13.7 | 43.7 | |
P<0.05 | P<0.005 | P<0.005 | |||||
Nutlin-3 | SKNAS | 1.4±0.3 | 1.5±0.6 | 1.5±0.7 | 1.3 | 1.2 | 1.2 |
P=0.321 | P=0.109 | P=0.225 | |||||
SHSY5Y | 2.4±0.2 | 1.9±0.4 | 1.4±0.3 | 2.1 | 2.8 | 3.7 | |
|
|
|
|
|
P<0.05 |
P<0.05 |
P<0.01 |
SKNBe2C | 2.2±0.5 | 1.2±0.2 | 0.7±0.2 | 13.0 | 23.5 | 42.4 | |
P<0.05 | P<0.05 | P<0.05 | |||||
NDD0005 | SKNAS | 1.0±0.1 | 0.8±0.1 | < 0.1 | 1.2 | 1.4 | ND |
P=0.1 | P<0.05 | ND | |||||
SHSY5Y | 2.3±0.7 | 0.5±0.1 | 0.2±0.1 | 2.4 | 12.0 | 33.1 | |
|
|
|
|
|
P<0.05 |
P<0.05 |
P<0.05 |
SKNBe2C | 22.8±3.2 | 3.1±0.6 | 1.0±0.1 | 1.92 | 13.9 | 44.4 | |
P<0.001 | P<0.01 | P<0.01 | |||||
MI-63 | SKNAS | 1.1±0.2 | 1.0±0.1 | 0.9±0.1 | 1.2 | 1.3 | 1.4 |
P=0.664 | P=0.377 | P=0.242 | |||||
SHSY5Y | 3.9±0.8 | 1.8±0.6 | 0.6±0.1 | 1.3 | 2.9 | 9.5 | |
|
|
|
|
|
P=0.096 |
P<0.001 |
P<0.01 |
SKNBe2C | 14.6±2.2 | 18.8±2.2 | 2±0.3 | 1.8 | 1.4 | 13.3 | |
P=0.073 | P=0.39 | P=0.052 | |||||
RG7388 | SKNAS | 1.2±0.1 | 1±0.002 | 0.9±0.1 | 1.0 | 1.1 | 1.2 |
P=0.532 | P=0.078 | P=0.06 | |||||
SHSY5Y | 2.6±0.4 | 2.3±0.2 | 1.1±0.5 | 2.0 | 2.2 | 4.8 | |
P<0.05 | P<0.05 | P<0.01 |
Abbreviations: MDR-1=Multi-Drug Resistance Protein 1; ND=not determined.
Values represent average±s.e.m.
For p53 mutant cells, verapamil, Nutlin-3, NDD0005, MI-63 and RG7388 were used at 1, 2 and 5 μM in combination with vincristine. For p53 wt cells, verapamil was used at 1, 2 and 5 μM in combination with vincristine, whereas Nutlin-3, NDD0005, MI-63 and RG7388 were used in combination at 0.25 × , 0.5 × and 1 × GI50 concentrations.