Fig. 5: Synergistic effect of EGFR TKI plus prednisone in immunocompetent transgenic mouse models (TGMM) and secondary resistant EGFR mutant models. | Nature Communications

Fig. 5: Synergistic effect of EGFR TKI plus prednisone in immunocompetent transgenic mouse models (TGMM) and secondary resistant EGFR mutant models.

From: Comprehensive targeting of resistance to inhibition of RTK signaling pathways by using glucocorticoids

Fig. 5

a–f EGFR L858R mutant transgenic mice and KRAS LSL-G12D mutant (EGFRwt) transgenic mice were generated as described in Methods. They were divided into four groups each strain (n = 3 for a and n = 3 for d without erlotinib; n = 4 for a and n = 5 for d with erlotinib) and received 5 mg/kg/day prednisone and erlotinib (6.25 or 100 mg/kg/day for EGFR mutant or wt) for 28 days. Tumor growth was monitored at the indicated days by magnetic resonance imaging (MRI). Representative images were shown. The white round structure at the bottom are hearts, labeling with “H”. Tumors are represented by white infiltrations around the hearts. Some representative tumors are pointed by arrows. Tumor sizes were calculated by ImageJ. The survival was recorded and drawn as Kaplan–Meier (KM) plots. g HCC827 derived erlotinib-resistant lines ER3, ER4A, ER4B, and ER5 were treated with 10 µM prednisolone and/or 1 µM erlotinib for 72 h. AlamarBlue assay was used to determine cell viabilities. N = 3 biological repeated experiments. h Similar experiment on EGFR L858R and T790M mutant H1975 cell line, where 10 nM osimertinib was used instead of erlotinib. N = 3 biological repeated experiments. i, j 1 million H1975 cells and 2 million HCC827 cells were s.c. injected into nude mice. Mice were divided into four groups (n = 6) and received the indicated treatments. k EGFR L858R mutant HCC4190 PDX were implanted into NOD-SCID mice. Mice were treated with the indicated drugs (n = 6 for each group). Xenograft and PDX sizes were measured by a caliper and shown as mean volume ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, by repeated measures (RM) two-way ANOVA, adjusted by Bonferroni’s test (ADIJK), two-way ANOVA adjusted by Bonferroni’s test (GH), and log-rank test (CF). The statistical analysis above was performed on Graphpad Prism 9.0.0. Source data are provided as a Source Data file. p = 0.005,3e−6,0.03,5e−7,4e−5 (a);0.004,1e−6 (d);3e−5,0.006,0.003,1e−4 (g),2e−5(h),0.04 (i),0.0008 (j),0.08,0.004 (k).

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