Enhanced gemcitabine-mediated cell killing of human lung adenocarcinoma by vector-based RNA interference against PLK1

被引:16
作者
Zhao, Xin-Yu [1 ,2 ]
Nie, Chun-Lai [1 ,2 ]
Liang, Shu-Fang [1 ,2 ]
Yuan, Zhu [1 ,2 ]
Deng, Hong-Xin [1 ,2 ]
Wei, Yu-Quan [1 ,2 ]
机构
[1] Sichuan Univ, W China Hosp, State Key Lab Biotherapy, 1 Keyuan 4th Rd, Chengdu 610041, Peoples R China
[2] Sichuan Univ, W China Hosp, Ctr Canc, Chengdu 610041, Peoples R China
关键词
RNA interference; Polo-like kinase; Gemcitabine; POLO-LIKE-KINASE; BREAST-CANCER; PROGNOSTIC-SIGNIFICANCE; EXPRESSION PATTERNS; PROSTATE-CANCER; EARLY EVENT; IN-VITRO; APOPTOSIS; POLO-LIKE-KINASE-1; CHEMOSENSITIVITY;
D O I
10.1016/j.biopha.2012.01.003
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
100103 [病原生物学]; 100218 [急诊医学];
摘要
Specific PLK1 silencing may be an effective gene therapy modality of treating PLK1-overexpressed cancers. In this study, we first explored the anticancer efficacy of three different short hairpin-expressing plasmids targeting PLK1 in animal model, and then determined the combination therapy effect of gemcitabine with PLK1-shRNA as an adjuvant. Transfection of the PLK1-shRNAs to A549 lung cancer cells induced significant PLK1 depletion, growth inhibition and apoptosis. In vivo administration of PLK1-shRNA constructs to tumor-bearing mice resulted in xenograft regression. Moreover, the combination of PLK1-shRNA plus low-dose gemcitabine (GEM) produced an additive antitumor activity on the lung tumors owing to an inhibition of cancer cell survival and augmented apoptosis. These results indicated a feasible bio-chemotherapeutic strategy for cancer. (C) 2012 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:597 / 602
页数:6
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