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From: Steve on 3 Aug 2008 01:52
http://www.ncbi.nlm.nih.gov/pubmed/18595135?ordinalpos=44&itool=EntrezSystem
2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

World J Gastroenterol. 2008 Jun 21;14(23):3681-92. Links

Experimental treatment of pancreatic cancer with two novel histone
deacetylase inhibitors.

Haefner M, Bluethner T, Niederhagen M, Moebius C, Wittekind C, Mossner J,
Caca K, Wiedmann M.
Department of Internal Medicine II, University of Leipzig,
Philipp-Rosenthal-Str. 27, Leipzig 04103, Germany.

AIM: To investigate in vitro and in vivo treatment with histone deacetylase
inhibitors NVP-LAQ824 and NVP-LBH589 in pancreatic cancer.

METHODS: Cell-growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in
vitro in 8 human pancreatic cancer cell lines using the
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In
addition, the anti-tumoral effect of NVP-LBH589 was studied in a chimeric
mouse model. Anti-tumoral activity of the drugs was assessed by
immunoblotting for p21(WAF-1), acH4, cell cycle analysis, TUNEL assay, and
immunohistochemistry for MIB-1.

RESULTS: In vitro treatment with both compounds significantly suppressed the
growth of all cancer cell lines and was associated with hyperacetylation of
nucleosomal histone H4, increased expression of p21(WAF-1), cell cycle
arrest at G2/M-checkpoint, and increased apoptosis. In vivo, NVP-LBH589
alone significantly reduced tumor mass and potentiated the efficacy of
gemcitabine. Further analysis of the tumor specimens revealed slightly
increased apoptosis and no significant reduction of cell proliferation.

CONCLUSION: Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active
against human pancreatic cancer, although the precise mechanism of in vivo
drug action is not yet completely understood. Therefore, further preclinical
and clinical studies for the treatment of pancreatic cancer are recommended.


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