Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Quan, P; Moinfar, F; Kufferath, I; Absenger, M; Kueznik, T; Denk, H; Zatloukal, K; Haybaeck, J.
Effects of targeting endometrial stromal sarcoma cells via histone deacetylase and PI3K/AKT/mTOR signaling.
Anticancer Res. 2014; 34(6):2883-2897
Web of Science
PubMed
- Führende Autor*innen der Med Uni Graz
- Haybäck Johannes
- Quan Ping
- Co-Autor*innen der Med Uni Graz
- Absenger-Novak Markus
- Denk Helmut
- Kolesnik Tatjana
- Moinfar Farid
- Zatloukal Kurt
- Altmetrics:
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- Plum Analytics:
- Abstract:
- Endometrial stromal sarcoma (ESS) is a rare gynecological mesenchymal malignancy with only few therapeutic options. This study aimed to investigate the efficacy of the histone deacetylase (HDAC) inhibitor suberanilohydroxamic acid (SAHA) combined with inhibitors of the phosphoinositid-3-Kinase (PI3K) pathway in ESS therapy. The effects of SAHA combined with inhibitor of PI3K (LY294002, LY), mammalian target of rapamycin mTOR (rapamycin), and their combination on cell growth and the PI3K pathway in two ESS cell lines (ESS-1 and MES-SA) and one non-neoplastic cell line HESC, were investigated. SAHA reduced growth of the three cell lines by inhibiting protein kinase B AKT and mTOR/p70S6K cascade activation. SAHA combined with LY or rapamycin, or both, synergistically reduced p-p70S6K and p-4E-BP1 levels. SAHA combined with LY and rapamycin led to the strongest growth inhibition and slowest growth recovery among the combination treatments. SAHA combined with inhibition of PI3K and mTOR could represent an efficient therapy option for patients with ESS. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Adaptor Proteins, Signal Transducing - metabolism
- Apoptosis - drug effects
- Blotting, Western -
- Cell Proliferation - drug effects
- Endometrial Neoplasms - drug therapy
- Endometrial Neoplasms - metabolism
- Endometrial Neoplasms - pathology
- Enzyme Inhibitors - pharmacology
- Female -
- Fluorescent Antibody Technique -
- Histone Deacetylases - chemistry
- Histone Deacetylases - metabolism
- Humans -
- Phosphatidylinositol 3-Kinases - antagonists & inhibitors
- Phosphatidylinositol 3-Kinases - metabolism
- Phosphoproteins - metabolism
- Proto-Oncogene Proteins c-akt - antagonists & inhibitors
- Proto-Oncogene Proteins c-akt - metabolism
- Ribosomal Protein S6 Kinases, 70-kDa - metabolism
- Sarcoma, Endometrial Stromal - drug therapy
- Sarcoma, Endometrial Stromal - metabolism
- Sarcoma, Endometrial Stromal - pathology
- Signal Transduction - drug effects
- TOR Serine-Threonine Kinases - antagonists & inhibitors
- TOR Serine-Threonine Kinases - metabolism
- Tumor Cells, Cultured -
- Find related publications in this database (Keywords)
- Endometrial stromal sarcoma
- SAHA
- PI3K/mTOR pathway
- combination therapy