Coadministration of conventional anti-cancer drugs enhances cell death in a p53-dependent manner.

(A) p53-positive (upper) or -negative (lower) HCT116 cells were treated with Cdc7-D or control siRNA for 24 hrs, followed by treatment with DMSO or 10 µM etoposide (Wako) for 32–40 hrs. (B) p53-positive (upper) or -negative (lower) HCT116 cells were treated with indicated chemicals (10 µM etoposide or 5FU (Wako) and 1 µM Cdc7 inhibitor (Calbiochem)) for 16 hrs. In A and B, DNA contents were analyzed by FACS (10,000 cells for each) and the fractions of sub-G1 population were calculated and presented. Synergistic effect of etoposide and 5FU on cell death induced by Cdc7 inhibition was observed in a p53-positive HCT116 but not in p53-negative HCT116. (C) Colony formation assays were conducted in p53-positive HCT116 cells. Cells treated with drugs for 16 hrs were collected and 500 cells were seeded in a 3.5 cm plate and cultured. The numbers of colonies were counted after 7 days. “n” represents the numbers of independent experiments conducted.