Source:http://linkedlifedata.com/resource/pubmed/id/19247395
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
|
| pubmed:dateCreated |
2009-8-17
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| pubmed:abstractText |
Oncogenic ras genes relate to the development of human cancers. In this study, we used a plasmid-mediated short-hairpin RNA (shRNA) targeting N-ras gene to combine with clinical drug vincristine (VCR) for the treatment of human hepatoma cells. Our results showed that anti-N-Ras shRNA expression vector (pCSH1-shNR) knocked down the target mRNA and protein. Higher efficacy on growth inhibition was observed when pCSH1-shNR was combined with VCR. This synergistic effect was associated with abrogation of VCR-induced overexpressions of P-glycoprotein and multidrug resistance-associated protein 1 by pCSH1-shNR through downregulations of N-Ras and total Ras. Western blot analysis showed that pCSH1-shNR-induced downregulations of N-Ras and total Ras were potentiated by VCR. Following Ras downregulation, phosphorylations of ERK1/2 and Akt were dramatically inhibited by combinatory treatment. The data showed that pCSH1-shNR-induced inhibition of nuclear factor-kappaB was enhanced by VCR. In addition, the combination of pCSH1-shNR and VCR synergistically inhibited the growth of human hepatoma HepG2 in vivo. Our findings suggested that combination of gene-specific therapeutics and appropriate chemotherapeutic agents might be a promising approach for the treatment of human hepatocellular carcinoma.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1476-5500
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
16
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
693-702
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| pubmed:meshHeading |
pubmed-meshheading:19247395-Animals,
pubmed-meshheading:19247395-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:19247395-Carcinoma, Hepatocellular,
pubmed-meshheading:19247395-Cell Line, Tumor,
pubmed-meshheading:19247395-Cell Proliferation,
pubmed-meshheading:19247395-Combined Modality Therapy,
pubmed-meshheading:19247395-Down-Regulation,
pubmed-meshheading:19247395-Female,
pubmed-meshheading:19247395-Gene Expression,
pubmed-meshheading:19247395-Gene Therapy,
pubmed-meshheading:19247395-Genes, ras,
pubmed-meshheading:19247395-Humans,
pubmed-meshheading:19247395-Liver Neoplasms,
pubmed-meshheading:19247395-MAP Kinase Signaling System,
pubmed-meshheading:19247395-Mice,
pubmed-meshheading:19247395-Mice, Inbred BALB C,
pubmed-meshheading:19247395-Mice, Nude,
pubmed-meshheading:19247395-Plasmids,
pubmed-meshheading:19247395-RNA Interference,
pubmed-meshheading:19247395-Vincristine,
pubmed-meshheading:19247395-Xenograft Model Antitumor Assays
|
| pubmed:year |
2009
|
| pubmed:articleTitle |
Suppression of N-Ras by shRNA-expressing plasmid increases sensitivity of HepG2 cells to vincristine-induced growth inhibition.
|
| pubmed:affiliation |
Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050, China.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|