WP1130 increases doxorubicin sensitivity in hepatocellular carcinoma cells through usp9x-dependent p53 degradation

Highlights • HCC cells with p53 expression displayed enhanced sensitivity. • p53 depletion abolished the synergistic cytotoxicity. • WP1130 co-treatment suppressed doxorubicin-mediated p53 upregulation. • usp9x downregulation abolished the synergistic cytotoxic effects of WP1130. • Tenovin-1 decreas...

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Veröffentlicht in:	Cancer letters 2015-06, Vol.361 (2), p.218-225
Hauptverfasser:	Liu, Hao, Chen, Wei, Liang, Chao, Chen, Bryan Wei, Zhi, Xiao, Zhang, Shufeng, Zheng, Xiaoxiao, Bai, Xueli, Liang, Tingbo
Format:	Artikel
Sprache:	eng
Schlagworte:	Antineoplastic Combined Chemotherapy Protocols - pharmacology Apoptosis Apoptosis - drug effects Cancer therapies Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Cell growth Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Cyanoacrylates Cytotoxicity DNA repair Doxorubicin - administration & dosage Doxorubicin - pharmacology Drug resistance Drug Resistance, Neoplasm Drug Synergism Enzymes Hematology, Oncology and Palliative Medicine Hep G2 Cells Hepatocellular carcinoma Humans Liver cancer Liver Neoplasms - drug therapy Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver Neoplasms - pathology Mortality Nitriles - administration & dosage Nitriles - pharmacology p53 Proteins Pyridines - administration & dosage Pyridines - pharmacology Rodents Signal Transduction Transfection Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Ubiquitin Thiolesterase - genetics Ubiquitin Thiolesterase - metabolism usp9x WP1130
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Beschreibung
Zusammenfassung:	Highlights • HCC cells with p53 expression displayed enhanced sensitivity. • p53 depletion abolished the synergistic cytotoxicity. • WP1130 co-treatment suppressed doxorubicin-mediated p53 upregulation. • usp9x downregulation abolished the synergistic cytotoxic effects of WP1130. • Tenovin-1 decreased the doxorubicin cytotoxicity in the presence of WP1130.
ISSN:	0304-3835 1872-7980
DOI:	10.1016/j.canlet.2015.03.001