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. 2023 Oct 10;14:6332. doi: 10.1038/s41467-023-41828-z

Fig. 2. Trametinib and Lestaurtinib combination is preferentially effective in mutant KRAS compared to wild type KRAS LUAD cells.

Fig. 2

A Effect of Trametinib (Tram) and Lestaurtinib (Lest) combination on cell viability of wild type (wt) KRAS (H1437, H2126, HCC78, H1993 and H1650) and mutant (mut) KRAS (H1792, H2009, A549, HCC44, H23 and H358) cells treated for 72 h treatment. Tram: 0.5 μM; Lest: 0.625 μM (data: mean +/− SD; test: one-way ANOVA, Tukey’s adjustment). B Effect of Tram and Lest combination on cell viability of mut KRAS LUAD cells (H1792, H2009 and A549) grown in 3D culture conditions (72 h drug treatment; n: 3 cell lines). Tram: 0.01–0.05 μM; Lest: 0.05–0.1 μM (data: mean +/− SD; test: one-way ANOVA, Tukey’s adjustment). C Representative images of mut KRAS LUAD cell lines in (B) exposed to the different treatments. Scale bar: 200 μm. D Percent fold change growth of H1792-derived tumors of mice (n: 8 tumors per group) treated with indicated drugs (data: mean +/− SEM; test: Kruskal–Wallis, Dunn’s adjustment). E Waterfall plot of tumors in (C) at the last day of experiment. Ctrl: untreated control; Tram: 1 mg/kg; Lest: 30 mg/kg; Combo: drug combination. F, G Western blot of cleaved PARP expression of mut KRAS (H1792, H2009 and A549; E) and wt KRAS (H1568, H1993 and H1437; F) cell lines 24 h after drug treatment (loading control: GAPDH).