Figure 8.

Combined CDK1/2 and EGFR inhibitors have a synergetic anti-cancer effect in vivo. (A and B) NCI-H1975 (A) or PC-9 (B) cells were utilized to performed CCK-8 assays as indicated. Data were represented as the means ± SD of three independent experiments. (C–E) JNJ-7706621 at 10 mg/kg (twice/week), AZD9291 at 2 mg/kg (twice/week), or the combination was administered twice a week via intraperitoneal injection to Nu/Nu mice bearing the NCI-H1975 cell line xenografts (n = 5/group). Combination treatment led to a statistically significant decrease in tumor growth compared with either single-agent treatment. Mice were sacrificed after 4 wk. Tumor images were acquired as shown in C. Tumor volumes (D) and tumor weights (E) were measured. Data points in D represent mean tumor volume ± SD, n = 5. Data points in E represent mean tumor weight ± SD, n = 5. Statistical analyses were performed with two-tailed paired t test. **P < 0.01; N.S. stands for no significant change. (F–H) Tumor growth assay of colon PDX xenografts in Nu/Nu mice treated with vehicle, JNJ-7706621 (10 mg/kg, twice/week), AZD9291 (2 mg/kg, twice/week), or the combination for the models in vivo. Mice were sacrificed after 4 wk. Tumor images were acquired as shown in F. Tumor volumes (G) and tumor weights (H) were measured. Data points in G represent mean tumor volume ± SD, n = 5. Data points in H represent mean tumor weight ± SD, n = 5. Statistical analyses were performed with two-tailed paired t test. **P < 0.01, ***P < 0.01; N.S. stands for no significant change. (I–N) Representative images of H&E, Cleaved caspase3, Ki67, USP37, ERK1/2, and p-ERK1/2 staining using colon PDX tissues from I. Scale bars, 50 μm. (J–N) Quantification of cleaved caspase3 (J), Ki67 (K), p-ERK1/2 (L), USP37 (M), and ERK1/2 (N). Statistical analyses were performed with two-tailed paired t test. **P < 0.01, ***P < 0.01; N.S. stands for no significant change.