Figure 7
Cooperative induction of DNA damage in vivo by WEE1 and CHK1 inhibitors. LoVo xenograft tumor-bearing mice were treated with 60 mpk MK-1775 BID for 2 days, 60 mpk MK-8776 BID for 2 days, or the combination of MK-1775 and MK-8776 each at 60 mpk BID for 2 days. Tumors were collected at 2, 24, and 48 hours following the final dose. A, LoVo tumor lysates were analyzed by Western blot for pCHK1S345. B, Tumor sections were fixed and analyzed by immunohistochemistry (IHC). Representative images for γH2AX at 2 hours and 48 hours post final dose are shown. C, Quantitative analysis of IHC for both phospho-CHK1S345 and γH2AX (n=3); one-way ANOVA analyses *P<0.05. **P<0.01, ***P<0.001.