FIGURE 6.

Additive cytotoxic effects of K-7174 and HDAC inhibitors. A, we cultured RPMI8226 cells with various concentrations of K-7174 in combination with 4-hydroperoxy cyclophosphamide (4-OHCY), melphalan (l-PAM), romidepsin, or vorinostat, and assessed for the cell viability after 72 h. Isobologram analysis was carried out using the CompuSyn software program to obtain the combination index (CI). The CI values of less than 1.0 and greater than 1.0 indicate synergism and antagonism, respectively, by definition (44). B, whole cell lysates were prepared simultaneously in the experiments described in panel A and subjected to immunoblotting for the expression of HDAC1, HDAC2, HDAC3, acetylated histone H3, and GAPDH (internal control).