Fig. 6: KRASG12C inhibition and mTORC1 inhibition cause synergistic reduction in cap-dependent translation.
From: Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer
a H1373 and H2122 cells were transfected with two different siRNAs targeting eIF4E or scramble (scr) siRNA and cultured for 24 h. Media was replaced with or without 100 nM RM-018 and cells were treated for an additional 48 h and analyzed by FACS to quantify annexin positive cells. Data are means ± SD for n = 3 experimental replicates. P values are shown and were calculated by one-way ANOVA and post-hoc Tukey’s test. b H1373 and H2122 cells were transfected with two different siRNAs targeting eIF4E or scramble (scr) siRNA and cultured for 24 h. Media was replaced with or without 100 nM RM-018 and cells were treated for an additional 48 h, and lysates were analyzed by immunoblot. c H1373 and H2122 cells were treated with 1 nM RMC-6272, 100 nM RM-018, or the combination for the indicated times, followed by incubation with m7GTP-conjugated beads, and lysates were probed by immunoblot in parallel with whole cell extracts (input). d H2122 cells were treated with 100 µM Z-VAD-FMK, 1 nM RMC-6272, 100 nM RM-018, or indicated combinations for 48 h, and lysates were analyzed by immunoblot.
