Figure 6

Potentiation of gemcitabine and camptothecin cytotoxicity and protein biomarker changes induced in HT29 cells by structurally diverse Chk1 inhibitors. A. Chemical structures of Chk1 inhibitors. B. Potentiation of gemcitabine (Gem) or camptothecin (CPT) cytotoxicity in HT29 cells following 72 hour exposure in combination with 300 nM V158411, LY2603618, MK-8776 or GNE-900. The potentiation factor (Pf) was calculated as GI₅₀ cytotoxic agent alone/GI₅₀ cytotoxic agent plus Chk1 inhibitor. Values represent the average of 3 determinations ± SD. C. Biomarker changes induced in response to gemcitabine plus Chk1 inhibitor treatment in HT29 colon carcinoma cells. HT29 colon cancer cells were exposed to 50 nM gemcitabine (+) for 16 hours followed by increasing concentrations of Chk1 inhibitor for a further 24 hours. Protein expression was characterized by immunoblotting. D. Biomarker changes induced in response to camptothecin plus Chk1 inhibitor treatment in HT29 colon carcinoma cells. HT29 colon cancer cells were exposed to 100 nM camptothecin for 16 hours followed by 100 or 300 nM Chk1 inhibitor for a further 24 hours.