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. 2024 Jan 31;84(7):1115–1132. doi: 10.1158/0008-5472.CAN-23-2504

Figure 3.

Figure 3. Efficacy of MRTX1133 on spheroid growth and PDAC PDX models. A, Effect of MRTX1133 on the growth of spheroids derived from the indicated PDAC cell lines in the absence and presence of MRTX1133 (500 nmol/L). Growth of spheroids were determined on the basis of the object area using IncuCyte S3. B, Effect of MRTX1133 on the growth of 1222 spheroids. C, Western blotting to compare the effect of MRTX1133 on the indicated proteins between the cells grown in 2D monolayer and 3D culture as spheroids. D, Effect of ITGB1 knockdown in combination with MRTX1133 on the growth of spheroids derived from 3226 cell line. The impact of everolimus (10 nmol/L) in combination with MRTX1133 (500 nmol/L) on the growth of spheroids derived from 1222 and 3226 cell lines based on live cell imaging. E, Immunoblotting to determine the effect of everolimus in combination with MRTX1133 on the phosphorylation status of S6 in spheroids derived from 1222 cells. F, Normalized tumor growth rate of 828, 3226, and 1222 PDX following vehicle and MRTX1133 (30 mg/kg) treatment, administered intraperitonially (four times a day) for the indicated number of days. G, Biochemical analysis from tumor tissues excised from 1222 PDX treated with MRTX1133 to determine its effect on the KRAS-mediated signaling pathways. H, Representative images for H&E staining and IHC to evaluate the effect of MRTX1133 on the phosphorylation of ERK1/2. Scale bar, 40 μm. Error bars from all growth curves indicate mean and SEM from triplicates and the experiment was done at two independent times. ***, P < 0.0001 as determined by two-way ANOVA.

Efficacy of MRTX1133 on spheroid growth and PDAC PDX models. A, Effect of MRTX1133 on the growth of spheroids derived from the indicated PDAC cell lines in the absence and presence of MRTX1133 (500 nmol/L). Growth of spheroids were determined on the basis of the object area using IncuCyte S3. B, Effect of MRTX1133 on the growth of 1222 spheroids. C, Western blotting to compare the effect of MRTX1133 on the indicated proteins between the cells grown in 2D monolayer and 3D culture as spheroids. D, Effect of ITGB1 knockdown in combination with MRTX1133 on the growth of spheroids derived from 3226 cell line. The impact of everolimus (10 nmol/L) in combination with MRTX1133 (500 nmol/L) on the growth of spheroids derived from 1222 and 3226 cell lines based on live cell imaging. E, Immunoblotting to determine the effect of everolimus in combination with MRTX1133 on the phosphorylation status of S6 in spheroids derived from 1222 cells. F, Normalized tumor growth rate of 828, 3226, and 1222 PDX following vehicle and MRTX1133 (30 mg/kg) treatment, administered intraperitonially (four times a day) for the indicated number of days. G, Biochemical analysis from tumor tissues excised from 1222 PDX treated with MRTX1133 to determine its effect on the KRAS-mediated signaling pathways. H, Representative images for H&E staining and IHC to evaluate the effect of MRTX1133 on the phosphorylation of ERK1/2. Scale bar, 40 μm. Error bars from all growth curves indicate mean and SEM from triplicates and the experiment was done at two independent times. ***, P < 0.0001 as determined by two-way ANOVA.