Linked Life Data

19925030

Source:http://linkedlifedata.com/resource/pubmed/id/19925030

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-11-20
pubmed:abstractText
Cyclooxygenase-2 (COX-2) and Protein kinase B (PKB/Akt) play a crucial role in the formation of many malignant tumors and have been shown to be the important therapeutic targets. In the present study, we examined immunohistochemical expression of phosphorylated Akt (p-Akt) and COX-2 in 45 gastric adenocarcinomas with different tumor grades. Then, adenovirus-mediated small hairpin RNA (shRNA) expression vectors rAd5-Akt1+COX-2 (rAd5-A+C) that target sequences of human COX-2 and Akt1 were used to examine the inhibitory effects on cell proliferation, invasion and apoptosis in SGC7901 gastric adenocarcinoma and U251 glioma cells. Cell growth was inhibited by over 70%, as indicated by a MTT assay, and was accompanied by G1/G0 phase arrest in the rAd5-A+C treated group, indicating poor cell growth activities. The number of cells invading through the matrigel in the rAd5-A+C treated group was significantly decreased (36.2+/-3.1) compared with that of the control group SGC7901 (105.0+/-4.0) and the nonsense sequence group rAd5-HK (102.5+/-6.4). In addition, the tumor volumes in the SGC7901 subcutaneous nude mouse model treated with rAd5-A+C was significantly smaller than those of the control group and nonsense sequence group rAd5-HK. When COX-2 and Akt1 were dramatically downregulated, Ki-67, CyclinD1, MMP-2, MMP-9 and Bcl-2 were also downregulated. Our results demonstrated that p-Akt and COX-2 were overexpressed in gastric adenocarcinomas and their expression levels were elevated with the ascending order of tumor malignancy; rAd5-A+C targeting COX-2 and Akt1 downregulated their expression significantly in a sequence-specific manner, exerting inhibitory effects on SGC7901 and U251 cell proliferation, invasion and apoptosis. In conclusion, our data suggest a novel mechanism for the regulation of malignant tumor cell growth and provide evidence for combined gene therapy for malignant tumors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1533-0338
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
467-78
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Expression of p-Akt and COX-2 in gastric adenocarcinomas and adenovirus mediated Akt1 and COX-2 ShRNA suppresses SGC-7901 gastric adenocarcinoma and U251 glioma cell growth in vitro and in vivo.
pubmed:affiliation
Gastroenterology, Tianjin Medical University General Hospital, 154 An-Shan Road, Heping District, Tianjin 300052, People's Republic of China.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't