Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 杜健华教授 (药剂学院) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1016/j.lungcan.2016.11.019 出版商提供的全文 http://www.sciencedirect.com/science/article/pii/S0169500216305359 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/0WOS source URL
Scopushttp://aims.cuhk.edu.hk/converis/portal/Publication/0Scopus source URL
其它资讯
摘要Objectives To investigate and elucidate the mechanism for the potentiation of cisplatin anticancer activity by belinostat in platinum (Pt)-resistant lung cancer cells. Materials and methods Combination of cisplatin and belinostat was investigated in two pairs of parental and cisplatin-resistant non-small cell lung cancer (NSCLC) cell lines. The Pt-resistant cell models exhibited overexpression of the efflux transporter ABCC2 and enhanced DNA repair capacity. Cellular accumulation of cisplatin and extent of DNA platination were measured by inductively coupled plasma optical emission spectrometer. Expression of Pt transporters and DNA repair gene were determined by quantitative real-time PCR. Inhibition of ABCC2 transport activity was examined by flow cytometric assay. Regulation of ABCC2 at the promoter level was studied by chromatin immunoprecipitation assay. Results and conclusion In Pt-resistant lung cancer cells, belinostat apparently circumvent the resistance through inhibition of both ABCC2 and DNA repair-mediated mechanisms. The combination of belinostat and cisplatin were found to display synergistic cytotoxic effect in cisplatin-resistant lung cancer cell lines when the two drugs were added concomitantly or when belinostat was given before cisplatin. Upon the concomitant administration of belinostat, cellular accumulation of cisplatin and formation of DNA-Pt adducts were found to be increased whereas expression levels of the efflux transporter ABCC2 and the DNA repair gene ERCC1 were inhibited in Pt-resistant cells. Belinostat-mediated downregulation of ABCC2 was associated with an increase association of a transcriptional repressor (negative cofactor 2) but reduced association of a transcriptional activator (TFIIB) to the ABCC2 promoter. The data advocates the use of belinostat as a novel drug resistance reversal agent for use in combination cancer chemotherapeutic regimens.
出版社接受日期27.11.2http://aims.cuhk.edu.hk/converis/portal/Publication/016
着者Kenneth Kin-Wah To, Wing-Sum Tong, Li-wu Fu
期刊名称Lung Cancer
出版年份2http://aims.cuhk.edu.hk/converis/portal/Publication/017
月份1
卷号1http://aims.cuhk.edu.hk/converis/portal/Publication/03
页次58 - 65
国际标準期刊号http://aims.cuhk.edu.hk/converis/portal/Publication/0169-5http://aims.cuhk.edu.hk/converis/portal/Publication/0http://aims.cuhk.edu.hk/converis/portal/Publication/02
电子国际标準期刊号1872-8332
语言美式英语
关键词Belinostat, Platinum anticancer drug, Drug resistance, Efflux transporters, DNA repair
