Table 1.

Concurrent MEK and mTOR inhibition is synergistic in human NSCLC cell lines

CellsP53B-RAFK-RASIC50 CI-1040 (μmol/L)IC50 PD0325901 (μmol/L)IC30 AP23573 (nmol/L)Mean CI (± SD; FA, 0.2–0.8)
Colo205Y103V600EWild-type0.31∼0.015.751.02 (±0.21)
H1755C242G469AWild-type2.4824.760.50 (±0.05)
H1395Wild-typeG469AWild-type6.4384.110.51 (±0.13)
H1666Wild-typeG466VWild-type5.420.57.830.21 (±0.15)
A549Wild-typeWild-typeG12S6.120.62.450.36 (±0.12)
H157 *, E298Wild-typeG12R13.5>40>200.97 (±0.55)
H1703 IntronicWild-typeWild-type12.6>408.830.72 (±0.24)
  • NOTE: Mutation data were from the COSMIC1 database. IC50 and IC30 are doses that result in 50% and 30% growth inhibition, respectively, relative to vehicle-only-treated control cells. Strict criteria were applied to drug interaction analyses, where synergism was defined as CI ≤ 0.7, additivity as 0.7 ≤ CI ≤ 1, and antagonism as CI ≥ 1. Data were expressed as mean CI (± SD), determined for a range of drug concentrations and a fractional effect (FA) of 0.2 to 0.8. Supporting data summarizing the nature of the drug interaction with dose range are presented in Supplementary Fig. S1 for some cell lines.

  • * PTEN G251C mutant.

  • CA-AKT.