Figure 6
V158411 potentiates the anti-tumor efficacy of cytotoxic chemotherapeutic drugs in vitro. A. Curves representing the 72 hour antiproliferative effect of gemcitabine (left) or cisplatin (right) in MDA-MB-468 cells in combination with 0, 0.2 or 0.4 μM V158411. B. In vitro potentiation of gemcitabine and cisplatin cytotoxicity by 0.1, 0.2, 0.4 or 0.8 μM V158411 in p53-proficient or p53-deficient breast cancer cell lines. Potentiation factor was calculated by IC50(cytotoxic agent alone)/IC50(combination treatment). C. In vitro potentiation of carboplatin, oxaliplatin and cisplatin cytotoxicity in SKOV-3 ovarian cancer cells by 0.1 μM V158411. The GI50 values are the average of 3 determinations ± SD with the potentiation factor highlighted above each bar. D. SKOV-3 cells were treated with 250 μM carboplatin, 80 μM oxaliplatin or 20 μM cisplatin for 24 hours in the presence of 0, 0.1 or 0.2 μM V158411 for 24 hours. The amount of Chk1 and H2AX phosphorylation was determined by western blotting.