Table 3. NEDD4 regulates [pemetrexed + sildenafil] lethality in part by modulating PTEN expression.
Afatinib resistant H1975 clones were transfected with a scrambled control siRNA or an siRNA to knock down the expression of NEDD4. In parallel the clones were transfected with a scrambled control siRNA or an siRNA to knock down the expression of PTEN. Twenty-four h later cells were treated with vehicle control or [pemetrexed (0.5 μM) + sildenafil (2.0 μM)]. Twenty-four h after treatment, cell viability was determined via live/dead assays (n = 3 +/-SEM)
| 24h | VEH | P+S | VEH | P+S | VEH | P+S | VEH | P+S |
|---|---|---|---|---|---|---|---|---|
| Death% | 1 | 38 ± 5.0 | 1 | 7 ± 1.6* | 1 | 78 ± 9.8# | 1 | 46 ± 5.3¶ |
| Death% | 1 | 35 ± 4.0 | 1 | 5 ± 0.8* | 1 | 56 ± 6.7# | 1 | 34 ± 4.2¶ |
| Death% | 1 | 36 ± 3.7 | 1 | 11 ± 2.0* | 1 | 50 ± 6.3# | 1 | 43 ± 4.8¶ |
| Death% | 1 | 45 ± 3.9 | 1 | 15 ± 2.5* | 1 | 66 ± 6.9# | 1 | 44 ± 4.1¶ |
| Death% | 1 | 34 ± 4.8 | 1 | 13 ± 2.1* | 1 | 58 ± 6.8# | 1 | 30 ± 3.6¶ |
| Afat-R | siSCR siSCR | SJNEDD4 SiSCR | siSCR siPTEN | siNEDD4 siPTEN | ||||
*
p < 0.05 less than values in siSCR + siSCR cells;
#
p < 0.05 greater than values in siSCR + siSCR cells;
¶
p < 0.05 less than values in siSCR + siPTEN cells.