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. 2022 Oct;8(6):a006222. doi: 10.1101/mcs.a006222

Figure 4.

Figure 4.

ROS1-directed targeted inhibitors target NOTCH1–ROS1-driven signaling and in vitro and in vivo oncogenic growth. (A) Ba/F3 proliferation assay using clinical ROS1-directed inhibitors in BA/F3 cell growth. (B) Soft agar colony formation analysis with NIH3T3 cell models in presence of increasing doses of entrectinib and crizotinib. n = 10, * denotes P-value ≤0.05 and ** denotes P-value ≤0.01. Western blot analysis of (C) Ba/F3 model and (D) NIH3T3 model upon treatment with crizotinib and entrectinib. (E) Tumor volume plot from in vivo flank xenograft of NOTCH1–ROS1 expressing NIH3T3 and vector control cells in NSG mice and bi-daily oral gavage treatment with entrectinib. n = 8 Significant decrease compared to * NOTCH1–ROS1 + Vehicle, ** NOTCH1–ROS1 + 15 mg/kg Entrectinib, *** NOTCH1–ROS1 + 30 mg/kg Entrectinib. (F) Western blot analysis of mouse tumor lysates to show targeting of MAPK, PI3K, and JAK/STAT and expression of fusion protein in the myc-tag blot.