Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Highly Accessed Research article

Experimental in vivo and in vitro treatment with a new histone deacetylase inhibitor belinostat inhibits the growth of pancreatic cancer

Dmitriy I Dovzhanskiy1, Stefanie M Arnold1, Thilo Hackert1, Ina Oehme2, Olaf Witt23, Klaus Felix1, Nathalia Giese1 and Jens Werner1*

Author Affiliations

1 Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

2 German Cancer Research Center (DKFZ), G340, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

3 Department of Pediatric Oncology, University of Heidelberg Medical Center, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany

For all author emails, please log on.

BMC Cancer 2012, 12:226  doi:10.1186/1471-2407-12-226

Published: 8 June 2012

Abstract

Background

Treatment options for pancreatic ductal adenocarcinoma (PDAC) are limited. Histone deacetylase inhibitors are a new and promising drug family with strong anticancer activity. The aim of this study was to examine the efficacy of in vitro and in vivo treatment with the novel pan-HDAC inhibitor belinostat on the growth of human PDAC cells.

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.

Results

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.

Conclusion

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.

Keywords:
Pancreatic cancer; Histone deacetylase inhibitors; Belinostat; Mice