Ping Quan1, Farid Moinfar2, Iris Kufferath1, Markus Absenger3, Tatjana Kueznik3, Helmut Denk1, Kurt Zatloukal1, Johannes Haybaeck4. 1. Institute of Pathology, Medical University of Graz, Graz, Austria. 2. Institute of Pathology, Medical University of Graz, Graz, Austria Department of Pathology, Hospital of the Sisters of Charity Linz, Linz, Austria. 3. Center for Molecular Research, Medical University of Graz, Graz, Austria. 4. Institute of Pathology, Medical University of Graz, Graz, Austria johannes.haybaeck@medunigraz.at.
Abstract
AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: SAHA combined with inhibition of PI3K and mTOR could represent an efficient therapy option for patients with ESS. Copyright
AIM: 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. MATERIALS AND METHODS: The effects of SAHA combined with inhibitor of PI3K (LY294002, LY), mammalian target of rapamycinmTOR (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. RESULTS: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. CONCLUSION:SAHA combined with inhibition of PI3K and mTOR could represent an efficient therapy option for patients with ESS. Copyright
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