Figure 7
Comparison of protein biomarker changes in p53 proficient and deficient colon cancer cell lines. A. Potentiation of the cytotoxicity of gemcitabine (Gem), camptothecin (CPT), cisplatin (CP) or oxaliplatin (OxPt) by 400 nM V158411 was determined in p53 mutant HT29 or p53 wild-type HCT116 colon cancer cells after 72 hours. GI50 and cGI50 were calculated from the dose response curves using XLFit. The potentiation factor (Pf) was calculated as GI50/cGI50. Protein biomarker changes were assessed in HCT116 cells treated with B. 50 to 800 nM gemcitabine or 120 nM camptothecin in combination with 0 (−) or 400 nM (+) V158411 for 24 hours or C. camptothecin plus 0 (−) or 400 nM (+) V158411 for various time combinations and dosing regimens. D. HT29 or HCT116 cells were treated with the single agent IC80 of camptothecin (HT29, 0.43 μM; HCT116, 0.44 μM) or oxaliplatin (HT29, 131 μM; HCT116, 74 μM) for 18 hours followed by DMSO (−) or 400 nM (+) V158411 for a further 24 hours. Protein expression was characterized by immunoblotting.