Experimental in vivo and in vitro treatment with a new histone deacetylase inhibitor belinostat inhibits the growth of pancreatic cancer
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 inhib...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
8 June 2012
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| In: |
BMC cancer
Year: 2012, Volume: 12 |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/1471-2407-12-226 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1186/1471-2407-12-226 Verlag, kostenfrei, Volltext: http://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-12-226 
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| Author Notes: | Dmitriy I. Dovzhanskiy, Stefanie M. Arnold, Thilo Hackert, Ina Oehme, Olaf Witt, Klaus Felix, Nathalia Giese and Jens Werner |
| Summary: | 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. |
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| Item Description: | Gesehen am 29.08.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/1471-2407-12-226 |