Title |
NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo
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Published in |
OncoTargets and therapy, April 2017
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DOI | 10.2147/ott.s130236 |
Pubmed ID | |
Authors |
Jianpo Lian, Dengqiang Lin, Xing Xie, Yunze Xu, Lieyu Xu, Li Meng, Yu Zhu |
Abstract |
Malignant pheochromocytoma (PCC) is a rare tumor with a very poor prognosis and no effective treatments. The aim of this study was to assess the efficacy of a novel second-generation synthetic heat-shock protein 90 (HSP90) inhibitor, NVP-AUY922, to treat malignant PCC in vitro and in vivo. Cell Counting Kit-8 (CCK-8) and Transwell assays were used to assess the effects of NVP-AUY922 on the proliferation and migration of the PCC cell line PC12. Flow cytometry was used to determine the effects of NVP-AUY922 on apoptosis and cell-cycle progression. Activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (PKB/AKT) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling was measured using a Western blot analysis. In vivo, a mouse xenograft model was used to test the effects of intraperitoneal injection of NVP-AUY922 on tumor growth. NVP-AUY922 was found to be cytotoxic in PC12 cells at lower concentrations compared with 17-allylamino-17-demethoxygeldanamcyin (17-AAG). NVP-AUY922 inhibited the proliferation of PC12 cells in a time- and concentration-dependent manner and decreased the rate of migration of PC12 cells. Furthermore, we found that HSP90 inhibition induced cell-cycle arrest and apoptosis. In vivo, administration of NVP-AUY922 reduced PCC tumor growth without significant weight loss. Finally, we observed the modulation of MEK/ERK and PI3K/AKT signaling in response to NVP-AUY922 exposure. NVP-AUY922 exhibits potent anti-PCC activities in vitro and in vivo and represents a promising therapeutic small molecule for treating malignant PCC. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 7 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 2 | 29% |
Student > Ph. D. Student | 1 | 14% |
Unspecified | 1 | 14% |
Professor > Associate Professor | 1 | 14% |
Student > Master | 1 | 14% |
Other | 0 | 0% |
Unknown | 1 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 2 | 29% |
Medicine and Dentistry | 2 | 29% |
Agricultural and Biological Sciences | 1 | 14% |
Unspecified | 1 | 14% |
Unknown | 1 | 14% |