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International Journal of Clinical Oncology

Erschienen in:

01.12.2011 | Original Article

Histone deacetylase inhibitor augments anti-tumor effect of gemcitabine and pegylated interferon-α on pancreatic cancer cells

verfasst von: Shuichi Iwahashi, Mitsuo Shimada, Tohru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Koji Sugimoto, Yu Saito

Erschienen in: International Journal of Clinical Oncology | Ausgabe 6/2011

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Abstract

Background

Histone deacetylase (HDAC) is strongly associated with epigenetic regulation and carcinogenesis, and its inhibitor can induce the differentiation or apoptosis of cancer cells.

Methods

We investigated the anticancer effects of the HDAC inhibitor valproic acid (VPA) in combination with gemcitabine (GEM), an antimetabolic, and pegylated interferon-α2b (PEG-IFN-α2b) in a human pancreatic cancer cell line using a cell proliferation assay. The gene expressions of HDAC1, MTA1, p21^Waf1, and HIF-1 were evaluated by reverse transcription-PCR.

Results

Valproic acid at 0.5 mM when used alone did not suppress cell proliferation. PEG–IFN-α2b at 10²E/ml weakly suppressed cell proliferation in both the BxPC3 (by 28%) and SUIT-2 (by 17%) human pancreatic cancer cell lines. GEM at 5 nM when used alone suppressed cell proliferation by 36 and 61% in the BxPC3 and SUIT-2 cell lines, respectively. The combination treatment of GEM + PEG–IFN-α2b strongly suppressed cell proliferation in the SUIT-2 (82%) and BxPC3 (51%) cell lines, which was further reinforced by the addition of VPA up to 88 and 67%, respectively. The combination treatment of GEM + PEG–IFN-α2b enhanced the expression of p21^Waf1, which was also reinforced by VPA.

Conclusion

VPA augmented the inhibitory effects of PEG–IFN-α2b alone or in combination with PEG–IFN-α2b and GEM on cell proliferation. Such inhibitory effects may be due to the up-regulation of p21^Waf1 expression.

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Titel: Histone deacetylase inhibitor augments anti-tumor effect of gemcitabine and pegylated interferon-α on pancreatic cancer cells
verfasst von: Shuichi Iwahashi
Mitsuo Shimada
Tohru Utsunomiya
Yuji Morine
Satoru Imura
Tetsuya Ikemoto
Hiroki Mori
Jun Hanaoka
Koji Sugimoto
Yu Saito
Publikationsdatum: 01.12.2011
Verlag: Springer Japan
Erschienen in: International Journal of Clinical Oncology / Ausgabe 6/2011
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-011-0246-y

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Histone deacetylase inhibitor augments anti-tumor effect of gemcitabine and pegylated interferon-α on pancreatic cancer cells