Hospital Universitario San Cecilio, Granada, Spain.
Cancer Lett. 2011 Feb 1;301(1):47-56. doi: 10.1016/j.canlet.2010.10.026. Epub 2010 Nov 19.
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 EGFR 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.
本研究旨在探讨 PARP-1 抑制是否能使肝癌细胞系对多柔比星治疗更敏感。PARP-1 抑制剂（ANI）的添加和稳定的 siRNA 耗竭都显著增强了所用 DNA 损伤剂诱导的生长抑制作用。这种效应与未修复的 DNA 积累有关，与 EGFR 和 Bcl-xL 基因表达的减少以及阳性 Annexin-V 染色有关。这些结果为 PARP-1 在肿瘤化疗耐药中的直接作用提供了新的证据，与它对涉及肿瘤存活的关键基因转录的影响有关。
