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学科主题临床医学
Knockdown of mutant K-ras expression by adenovirus-mediated siRNA inhibits the in vitro and in vivo growth of lung cancer cells
Zhang, Zhiping; Jiang, Guanchao; Yang, Fan; Wang, Jun
关键词K-ras Non-small Cell Lung Cancer Sirna Rnai Apoptosis Adenovirus Gene Therapy
刊名CANCER BIOLOGY & THERAPY
2006-11-01
5期:11页:1481-1486
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]SMALL INTERFERING RNAS ; PANCREATIC-CANCER ; GENE-EXPRESSION ; ONCOGENIC RAS ; APOPTOSIS ; MICE ; TUMORIGENICITY ; PROLIFERATION ; ANGIOGENESIS ; SUPPRESSION
英文摘要

The ras mutation, which is observed in 20 - 30% of human nonsmall cell lung cancers (NSCLCs), is one of common genetic alterations and has been proposed to be a prognostic factor in lung cancer. Oncogene ras appears to be essential for tumor progression and maintenance. Several therapeutic agents have been developed to inhibit ras, such as FTIs and antisense oligonucleotides. A new tool for blocking oncogenes in cancer cells has emerged with the discovery that RNA interference can specifically silence expression of endogenous human genes. In the current study, we used small interfering RNA ( siRNA) directed against mutant K-ras to determine the anti-tumor effects of decreasing the levels of this protein in lung cancer cell lines. Adenovirus-mediated siRNA (AdH1/siK-ras(V12)) against K-ras(V12) markedly decreased K-ras(V12) gene expression and inhibited cellular proliferation of NSCLC H441 cells that express the relevant mutation (K-ras codon 12 GGT --> GTT), but produced minimal growth inhibition on NSCLC H1650 cells that lack the relevant mutation. Pretreatment with AdH1/siK-ras(V12) completely abrogated subcutaneous engraftment of H441 cells, as compared with a 100% tumor take in animals that received control vector-treated tumor cells. The in vivo effect of AdH1/siK-ras(V12) treatment was further examined by intratumoral injections after tumor induction. Pre-existing tumor growth was reduced by 45% by a single intratumoral injection. Three or five repeat injections resulted in complete tumor regression in eight of ten nude mice. Further, 23.12% of AdH1/siK-ras(V12) treated H441 cells underwent apoptosis, as compared with 6.13%, and 8.27% in untreated and control vector-treated cells, respectively. These results indicate that adenovirus-mediated siRNA can specifically and efficiently target factors whose expression is altered in malignancy and may have the potential as a therapeutic modality to treat human lung cancer.

语种英语
WOS记录号WOS:000243256800012
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被引频次:33[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50029
专题北京大学第二临床医学院_胸外科
作者单位Peking Univ, Peoples Hosp, Dept Thorac Surg, Beijing 100044, Peoples R China
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Zhang, Zhiping,Jiang, Guanchao,Yang, Fan,et al. Knockdown of mutant K-ras expression by adenovirus-mediated siRNA inhibits the in vitro and in vivo growth of lung cancer cells[J]. CANCER BIOLOGY & THERAPY,2006,5(11):1481-1486.
APA Zhang, Zhiping,Jiang, Guanchao,Yang, Fan,&Wang, Jun.(2006).Knockdown of mutant K-ras expression by adenovirus-mediated siRNA inhibits the in vitro and in vivo growth of lung cancer cells.CANCER BIOLOGY & THERAPY,5(11),1481-1486.
MLA Zhang, Zhiping,et al."Knockdown of mutant K-ras expression by adenovirus-mediated siRNA inhibits the in vitro and in vivo growth of lung cancer cells".CANCER BIOLOGY & THERAPY 5.11(2006):1481-1486.
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