Experimental in vivo and in vitro treatment with a new histone deacetylase inhibitor belinostat inhibits the growth of pancreatic cancer. Full Text
BMC Cancer, 06/13/2012
Dovzhanskiy DI et al. – Experimental treatment of human PDAC cells with belinostat is effective in vitro and in vivo and may enhance the efficacy of gemcitabine. A consecutive study of belinostat in pancreatic cancer patients alone, and in combination with gemcitabine, could further clarify these effects in the clinical setting.Methods
- The proliferation of tumour cell lines (T3M4, AsPC-1 and Panc-1) was determined using an MTT assay.
- Apoptosis was analysed using flow cytometry. Furthermore, p21Cip1/Waf1 and acetylated histone H4 (acH4) expression were confirmed by immunoblot analysis.
- The in vivo effect of belinostat was studied in a chimeric mouse model.
- Antitumoural activity was assessed by immunohistochemistry for Ki-67.
- Treatment with belinostat resulted in significant in vitro and in vivo growth inhibition of PDAC cells.
- This was associated with a dose-dependent induction of tumour cell apoptosis.
- The apoptotic effect of gemcitabine was further enhanced by belinostat.
- Moreover, treatment with belinostat increased expression of the cell cycle regulator p21Cip1/Waf1 in Panc-1, and of acH4 in all cell lines tested.
- The reductions in xenograft tumour volumes were associated with inhibition of cell proliferation.