Abstract 2557: Preclinical synergy of Plk1 inhibitors and HDACIs

Abstract Our laboratory is interested in the synergy between spindle check point inhibitors and histone deacetylase inhibitors (HDACIs). Previous work investigated two polo-like kinase inhibitors in prostate cancer and in non-small cell lung cancer (NSCLC). In preliminary studies we have investigated two polo-like kinase inhibitors, BI2536 and BI6727, in NSCLC cell lines H358 and H1838. In MTS proliferation assays, we found a significant inhibition of proliferation (For H358 the IC50 = 100nM for BI2536and BI672; and for H1838 the IC50 = 25nM for BI2536 and 50nM for BI6727). In clonogenic assays both polo-like kinase inhibitors caused a dose dependent inhibition of proliferation and survival in NSCLC. We explored these findings further with western blot analysis and found that both compounds arrested both cell lines in G2/M transition with elevated phosphorylated histone H3 and elevated cyclin B1. These findings show that polo-like kinase can be effectively targeted in NSCLC by these compounds. Given other studies in lung and prostate demonstrating down regulation of mitotic spindle proteins upon treatment with HDACIs, we plan to combine polo-like kinase inhibitors and HDACIs to investigate for additive or synergistic effects in NSCLC cell lines as has been seen in prostate cancer cell lines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2557. doi:10.1158/1538-7445.AM2011-2557