Reversal of platinum drug resistance by the histone deacetylase inhibitor belinostat

Highlights • Combination of cisplatin and belinostat is synergistic in NSCLC. • Belinostat apparently circumvent cisplatin resistance. • Belinostat increased cellular cisplatin accumulation by inhibiting ABCC2 efflux. • Belinostat downregulated ABCC2 by increasing binding of a repressor to the promo...

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Veröffentlicht in:	Lung cancer (Amsterdam, Netherlands) Netherlands), 2017-01, Vol.103, p.58-65
Hauptverfasser:	To, Kenneth Kin-Wah, Tong, Wing-Sum, Fu, Li-wu
Format:	Artikel
Sprache:	eng
Schlagworte:	Antineoplastic Agents - administration & dosage Antineoplastic Agents - metabolism Antineoplastic Agents - pharmacology Belinostat Cell Line - drug effects Cell Line - metabolism Cisplatin - administration & dosage Cisplatin - metabolism Cisplatin - pharmacology DNA Adducts DNA repair DNA Repair - drug effects Drug Administration Schedule Drug resistance Drug Resistance, Neoplasm Drug Synergism Drug Therapy, Combination - methods Efflux transporters Hematology, Oncology and Palliative Medicine Histone Deacetylase Inhibitors - administration & dosage Histone Deacetylase Inhibitors - metabolism Histone Deacetylase Inhibitors - pharmacology Humans Hydroxamic Acids - administration & dosage Hydroxamic Acids - metabolism Hydroxamic Acids - pharmacology Lung Neoplasms - drug therapy Multidrug Resistance-Associated Proteins - drug effects Multidrug Resistance-Associated Proteins - genetics Phosphoproteins - drug effects Phosphoproteins - genetics Platinum - administration & dosage Platinum - blood Platinum - metabolism Platinum - pharmacology Platinum anticancer drug Pulmonary/Respiratory Sulfonamides - administration & dosage Sulfonamides - metabolism Sulfonamides - pharmacology Transcription Factor TFIIB - drug effects Transcription Factor TFIIB - genetics Transcription Factors - drug effects Transcription Factors - genetics
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Zusammenfassung:	Highlights • Combination of cisplatin and belinostat is synergistic in NSCLC. • Belinostat apparently circumvent cisplatin resistance. • Belinostat increased cellular cisplatin accumulation by inhibiting ABCC2 efflux. • Belinostat downregulated ABCC2 by increasing binding of a repressor to the promoter. • Belinostat inhibited DNA repair by downregulating the DNA repair gene ERCC1.
ISSN:	0169-5002 1872-8332
DOI:	10.1016/j.lungcan.2016.11.019