The combination of the histone-deacetylase inhibitor trichostatin A and gemcitabine induces inhibition of proliferation and increased apoptosis in pancreatic carcinoma cells

  • Authors:
    • Susanne Gahr
    • Matthias Ocker
    • Marion Ganslmayer
    • Steffen Zopf
    • Kinya Okamoto
    • Andrea Hartl
    • Sandra Leitner
    • Eckhart G. Hahn
    • Christoph Herold
  • View Affiliations

  • Published online on: September 1, 2007     https://doi.org/10.3892/ijo.31.3.567
  • Pages: 567-576
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Abstract

The prognosis of advanced pancreatic cancer is poor. Established chemotherapy shows only limited efficacy and significant side effects. We investigated how far a combination of trichostatin A (TSA) and gemcitabine synergizes to inhibit proliferation and promotion of apoptosis of pancreatic adenocarcinoma cells in vitro. The human pancreatic carcinoma cells YAPC, DANG and Panc-89 and primary human foreskin fibroblasts as non-malignant controls were cultured under standardized conditions and incubated with gemcitabine und TSA alone (10−4 to 10−8 M) or together (10−6 to 10−7 M). After 24-72 h the apoptotic rate was analyzed by flow cytometry (propidium iodide, FACS). DNA-synthesis was assessed using bromodeoxyuridine (BrdU) incorporation. Protein was separated for Western blotting against caspase-3 and -8, p21, bax and bcl-2. The combination of TSA und gemcitabine leads to better pro-apoptotic effects than the employment of single substances. Bcl-2, a mitochondrial protein, which protects against apoptosis, was not expressed. Bax, an apoptosis inducing protein, which destabilizes the mitochondrial membrane potential, was increasingly expressed. Combination of TSA and gemcitabine shows promise for treatment of pancreatic cancer in vivo.

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September 2007
Volume 31 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Gahr, S., Ocker, M., Ganslmayer, M., Zopf, S., Okamoto, K., Hartl, A. ... Herold, C. (2007). The combination of the histone-deacetylase inhibitor trichostatin A and gemcitabine induces inhibition of proliferation and increased apoptosis in pancreatic carcinoma cells. International Journal of Oncology, 31, 567-576. https://doi.org/10.3892/ijo.31.3.567
MLA
Gahr, S., Ocker, M., Ganslmayer, M., Zopf, S., Okamoto, K., Hartl, A., Leitner, S., Hahn, E. G., Herold, C."The combination of the histone-deacetylase inhibitor trichostatin A and gemcitabine induces inhibition of proliferation and increased apoptosis in pancreatic carcinoma cells". International Journal of Oncology 31.3 (2007): 567-576.
Chicago
Gahr, S., Ocker, M., Ganslmayer, M., Zopf, S., Okamoto, K., Hartl, A., Leitner, S., Hahn, E. G., Herold, C."The combination of the histone-deacetylase inhibitor trichostatin A and gemcitabine induces inhibition of proliferation and increased apoptosis in pancreatic carcinoma cells". International Journal of Oncology 31, no. 3 (2007): 567-576. https://doi.org/10.3892/ijo.31.3.567