STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma

Background: Signal transducer and activator of transcription 3 (STAT3) regulates the expression of genes that mediate cell survival, proliferation, and angiogenesis and is aberrantly activated in various types of malignancies, including renal cell carcinoma (RCC). We examined whether it could be a n...

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Veröffentlicht in:	British journal of cancer 2010-05, Vol.102 (11), p.1592-1599
Hauptverfasser:	Horiguchi, A, Asano, T, Kuroda, K, Sato, A, Asakuma, J, Ito, K, Hayakawa, M, Sumitomo, M
Format:	Artikel
Sprache:	eng
Schlagworte:	631/154/436/2388 692/699/67/589/1588/1351 Angiogenesis Animals Antibodies Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Apoptosis Apoptosis - drug effects Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Cancer therapies Carcinoma, Renal Cell - drug therapy Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - metabolism Cell culture Cell cycle Cell Proliferation - drug effects Cell Survival - drug effects Cells, Cultured Cytokines Drug Resistance Epidemiology Gene Expression Regulation, Neoplastic - drug effects Humans Hypoxia-Inducible Factor 1, alpha Subunit - genetics Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Kidney cancer Kidney Neoplasms - drug therapy Kidney Neoplasms - genetics Kidney Neoplasms - metabolism Kidneys Kinases Medical prognosis Medical research Medical sciences Mice Mice, Nude Molecular Medicine Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - pathology Nephrology. Urinary tract diseases Oncology Phosphorylation Proteins Pyridines - pharmacology Pyridines - therapeutic use STAT3 Transcription Factor - antagonists & inhibitors Translational Therapeutics Tumors Tumors of the urinary system Tyrphostins - pharmacology Tyrphostins - therapeutic use Vascular endothelial growth factor Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - metabolism Xenograft Model Antitumor Assays
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Zusammenfassung:	Background: Signal transducer and activator of transcription 3 (STAT3) regulates the expression of genes that mediate cell survival, proliferation, and angiogenesis and is aberrantly activated in various types of malignancies, including renal cell carcinoma (RCC). We examined whether it could be a novel therapeutic target for RCC by using the STAT3 inhibitor WP1066. Methods: The antitumour activities and related mechanisms of WP1066 were investigated in vitro on renal cancer cell lines and in vivo on murine xenografts. Results: In Caki-1 and 786-O renal cancer cells, 5 μ M WP1066 prevented the phosphorylation of STAT3, and 2.5 μ M WP1066 significantly ( P
ISSN:	0007-0920 1532-1827
DOI:	10.1038/sj.bjc.6605691