Fig. 7.

Synergy of PLK-1 inhibition by BI-2536 with MDM2 inhibition by nutlin-3: Since PLK-1 plays a role in controlling p53 directly and via MDM2, we wanted to determine whether inhibition of PLK-1 would show synergy with MDM2 inhibition. a, b Indeed treatment of H295R (a) and SW-13 (b) cells with nutlin-3 and BI-2536 sensitized both the cell lines to nutlin-3. We also anticipated that dual inhibition of PLK-1 and MDM2 would result in a synergistic apoptotic response via p53. c, d Dual inhibition of PLK-1 and MDM2 resulted in an additive response in the H295R cells (c), with wild-type p53, whereas no additive apoptotic response was seen in the SW-13 cells (d) with mutant p53. Doxorubicin was used as a positive control for apoptosis. All experiments were done at least three individual times and data are represented as means with standard error