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

• Verfasst von: Dovzhanskiy, Dmitriy I. [VerfasserIn]
• Verfasst von: Arnold, Stefanie M. [VerfasserIn]
• Verfasst von: Hackert, Thilo [VerfasserIn]
• Verfasst von: Oehme, Ina [VerfasserIn]
• Verfasst von: Witt, Olaf [VerfasserIn]
• Verfasst von: Felix, Klaus M. [VerfasserIn]
• Verfasst von: Giese, Nathalia [VerfasserIn]
• Verfasst von: Werner, Jens [VerfasserIn]
• Titel: Experimental in vivo and in vitro treatment with a new histone deacetylase inhibitor belinostat inhibits the growth of pancreatic cancer
• Verf.angabe: Dmitriy I. Dovzhanskiy, Stefanie M. Arnold, Thilo Hackert, Ina Oehme, Olaf Witt, Klaus Felix, Nathalia Giese and Jens Werner
• E-Jahr: 2012
• Jahr: 8 June 2012
• Umfang: 9 S.
• Fussnoten: Gesehen am 29.08.2018
• Titel Quelle: Enthalten in: BMC cancer
• Ort Quelle: London : BioMed Central, 2001
• Jahr Quelle: 2012
• Band/Heft Quelle: 12(2012) Artikel-Nummer 226, 9 Seiten
• ISSN Quelle: 1471-2407
• DOI: doi:10.1186/1471-2407-12-226
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1580494560

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.