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. 2014 Jul 3;5(14):5674–5685. doi: 10.18632/oncotarget.2158

Figure 2. ATR inhibition sensitizes lung cancer cells to DNA damaging agents.

Figure 2

(A) Analysis of shifts in the concentration of DNA damaging agent required to inhibit cell viability by 50% (IC50) was used to determine the synergistic or antagonistic effects of a DDR inhibitor. Heat map representing the IC50 shift with the largest absolute value observed with VX-970 or AZD7762 in combination with cisplatin, etoposide, gemcitabine, oxaliplatin and irinotecan across a panel of 36 lung cell lines at 96 h. The colors represent a shift range from −10 (antagonism-blue) to +10 (synergy-red). (B) Histograms showing the percentage of cell lines with > 3-fold (top panel) or 10-fold (bottom panel) synergy with VX-970 (ATR) or AZD7762 (Chk1/2) in combination with cisplatin, oxaliplatin, irinotecan, gemcitabine and etoposide. (C) Impact of p53 on response to VX-970 in A549 cells. Histogram depicts maximum IC50 shift in vector control and p53 knockdown cells observed with VX-970 in combination with cisplatin, etoposide, gemcitabine, oxaliplatin and irinotecan.