HDAC gene expression in pancreatic tumor cell lines following treatment with the HDAC inhibitors panobinostat (LBH589) and trichostatine (TSA)

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Mehdi Ouaissi (Author) Other; Francoise Silvy (Author) Other; Sofia Costa Lima (Author) Other; Urs Giger (Author) Other; Kevin Zemmour (Author) Other; Bernard Sastre (Author) Other; Igor Sielezneff (Author) Other; Anabela Cordeiro da Silva (Author) FFUP; Dominique Lombardo (Author) Other; Eric Mas (Author) Other; Ali Ouaissi (Author) Other

Journal

Title: Pancreatology

Vol. 12

Pages: 146-155

ISSN: 1424-3903

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 15 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-002-CBY

DOI: 10.1016/j.pan.2012.02.013

Abstract (EN): Background: In this study, the effect of LBH589 and trichostatin (TSA), a standard histone deacetylase inhibitor (HDACi) toward the growth of pancreatic cancer cell lines was studied. Thus, we examined for the first time, the HDAC family gene expression levels before and after drug treatment. Methods: Several human pancreatic cancer cell lines (Panc-1, BxPC-3, SOJ-6) and a normal human pancreatic duct immortalized epithelial cell line (HPDE/E6E7) were used as target cells. The cell growth was measured by mu assay, cell cycle alteration, membrane phosphatidylserine exposure, DNA fragmentation, mitochondrial membrane potential loss, RT-PCR and Western blots were done using standard methods. The effect of drugs on tumor growth in vivo was studied using subcutaneous xenograft model. Results: Except in the case of certain HDAC gene/tumor cell line couples: (SIRT1/HPDE-SOJ6/TSA- or LBH589-treated cells; LBH589-treated Panc-1 Cells; HDAC2/BxPC-3/LBH589-treated cells or TSA-treated SOJ-6-1 cells), there were no major significant changes of HDACs genes transcription in cells upon drug treatment. However, significant variation in HDACs and SIRTs protein expression levels could be seen among individual cell samples. The in vivo results showed that LBH589 formulation exhibited similar tumor reduction efficacy as the commercial drug gemcitabine. Conclusion: Our data demonstrate that LBH589 induced the death of pancreatic tumor cell by apoptosis. In line with its in vitro activity. LBH589 achieved a significant reduction in tumor growth in BxPC-3 pancreatic tumor cell line subcutaneous xenograft mouse model. Furthermore, exploring the impact of LBH589 on HDACs encoding genes expression revealed for the first time that some of them, depending on the cell line considered, seem to be regulated during translation. Copyright

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10