Inhibition of poly (ADP-ribose) polymerase-1 enhances doxorubicin activity against liver cancer cells

Inhibition of poly (ADP-ribose) polymerase-1 enhances doxorubicin activity against liver cancer cells
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DOI:
10.1016/j.canlet.2010.10.026
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发表时间:
2011-02-01
期刊:
影响因子:
9.7
通讯作者:
Salmeron, J.
Salmeron, J.
中科院分区:
医学1区
文献类型:
--
作者:
Munoz-Gamez, J. A.;Quiles-Perez, R.;Salmeron, J.

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本研究的目的是研究PARP-1抑制是否使人肝癌细胞系对阿霉素治疗敏感。添加PARP-1抑制剂(ANI)和通过稳定的siRNA的消耗都显著增强了由所使用的DNA损伤剂诱导的生长抑制。这种效应与未修复DNA的积累、埃格和Bcl-xL基因表达的减少以及膜联蛋白V染色阳性有关。这些结果提供了新的证据,表明PARP-1在肿瘤化疗耐药性中的直接作用与其对参与肿瘤生存的关键基因转录的影响有关。(C)2010爱思唯尔爱尔兰有限公司版权所有。
The purpose of this study was to investigate whether PARP-1 inhibition sensitizes human liver cancer cell lines to doxorubicin treatment. Both the addition of PARP-1 inhibitor (ANI) and depletion by means of stable siRNA significantly enhanced the growth inhibition induced by the DNA damage agents used. This effect was associated with an accumulation of unrepaired DNA, with a reduction in EGER and Bcl-xL gene expression as well as with positive annexin-V staining. These results provide novel evidence of the direct role of PARP-1 in tumour chemoresistance in relation to its effects on the transcription of key genes involved in tumour survival. (C) 2010 Elsevier Ireland Ltd. All rights reserved.