Fig. 8: Small molecule inhibitors of Chk1 and ATM cooperate with each other to preferentially inhibit proliferation of H1975 xenograft tumors with mutant p53.

Scatter plots of tumor weights from xenografts of H1975 (A) shGFP and B shp53 cells after indicated vehicle or drug treatments. Seven mice were used in each group. p values (two-tailed t test) are shown. TUNEL assay for apoptosis (C) in tumors from (A and B). Representative images (Magnification ×20) and Swarm plot (lower panel) of vehicle (–), Chk1i and/or ATMi -treated tumor sections from H1975 shGFP and shp53 xenografts show apoptotic cells (green fluorescence) by TUNEL assay. At least 10 blind images were used. Representative data from three different mice tumor sections were counted. p values are shown. D Representative image of anti-p53 immunostaining and DAPI staining of FFPE lung tumor or lung tissue sections after vehicle- or ATMi/Chk1i-treatment (oral or nasal) from orthotopic H1975 xenograft tumors expressing luciferase (Fig. S7). E Scatter plots show the percentage of normal mitotic cells in (D). F Whole slide images of lung tumors after H&E staining, Ki67 or c-Caspase 3 immunostaining, and QuPath image (Green: stroma, dark red, tumor, blue normal lung tissue). Scatter plots (bottom panel) show the percentage of (G) Ki67 and H c-caspase 3 positive cells in (F) from tumors of two mice. p values are shown.