A. BI-2536 attenuates DLD-1 tumor growth in vivo. Intravenous injection of BI-2536 started 1 week after subcutaneous injection of DLD1 cells. Tumor volume at each time point was normalized to the initial tumor volume (* p<0.05 and ** p<0.01, 2-way ANOVA, error bars indicate S.E.M.). Representative images of tumors after treatment are shown.
B. BI-2536 attenuates HCT116 tumor growth in vivo. Treatment of HCT116 xenografts was similar to that described for DLD-1 tumors (* p<0.05 and ** p<0.01, 2-way ANOVA, error bars indicate S.E.M.).
C. A model in which oncogenic Ras introduces mitotic stress that can be exacerbated to produce lethality by interfering with kinetochore and APC/C function. Genes shaded green are RSL genes, while yellow genes cause Ras-specific lethality when overproduced. Dotted lines illustrate hypothetical connections between Ras and aspects of mitotic regulation leading to mitotic stress.
D. Sensitivity of a panel of NSCLCs to APC/C shRNAs. NSCLCs with endogenous Ras mutations (H23, H358, H647, H1299, H1734, H2030, H2122 and H2228) and without Ras mutations (H522, H838, H1437, H1650, H1838 and H1975) were infected with shRNAs against APC1 or APC4. Cell viability was compared to control FF shRNA infected samples 6 days post infection.