The combination of the histone-deacetylase inhibitor trichostatin A and gemcitabine induces inhibition of proliferation and increased apoptosis in pancreatic carcinoma cells
| Autor: | Steffen Zopf, Andrea Hartl, Eckhart G. Hahn, Marion Ganslmayer, Sandra Leitner, Matthias Ocker, Kinya Okamoto, S Gahr, Christoph Herold |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Programmed cell death Pancreatic disease medicine.drug_class Apoptosis Cell Separation Biology Hydroxamic Acids Deoxycytidine Proto-Oncogene Proteins p21(ras) chemistry.chemical_compound Cell Line Tumor Pancreatic cancer Antineoplastic Combined Chemotherapy Protocols medicine Humans Propidium iodide Cell Proliferation bcl-2-Associated X Protein Caspase 8 Caspase 3 Carcinoma Histone deacetylase inhibitor Flow Cytometry medicine.disease Gemcitabine Pancreatic Neoplasms Trichostatin A Proto-Oncogene Proteins c-bcl-2 Oncology chemistry Cancer research medicine.drug |
| Zdroj: | International Journal of Oncology. |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.31.3.567 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|