Table 3.

Cooperative suppression of ribosomal biosynthesis and translation by combined MEK and mTOR inhibition

TreatmentRelative % ribosomes (±SE)P/M ratio (±SE)
3 h (n = 6)24 h (n = 4)3 h (n = 5)24 h (n = 5)
Control1001003.86 ± 0.563.39 ± 0.36
CI-1040 (2 μmol/L)99.2 ± 7.296.3 ± 7.83.52 ± 0.813.11 ± 0.39
AP23573 (3 nmol/L)92.8 ± 10.684.7 ± 10.73.59 ± 0.703.04 ± 0.42
Combination91.5 ± 8.9NS58.9 ± 3.3 *3.40 ± 0.51NS2.60 ± 0.38
  • NOTE: Asynchronous A549 cells were treated with CI-1040 and AP23573 alone, and in combination, at doses that were synergistic. Total ribosomes were isolated and quantified, as described in Materials and Methods. Equal quantities of total ribosomes and/or S = 30 protein were resolved on 15% to 50% sucrose gradients to generate P/M profiles for each drug treatment ( Fig. 2D). The P/M ratio, an index of translational efficiency, was determined as the ratio of the areas of translated polysomes to the areas of untranslated monosomes, using NIH image J. Statistical significance (two-tailed paired and unpaired Student's t tests to analyze P/M ratios and % ribosomes, respectively) is indicated for combination treatments relative to CI-1040 and AP23573 alone.

  • Abbreviation: NS, not significant.

  • * P < 0.05.

  • P < 0.01.