A double suicide gene system driven by KDR promoter selectively kills human hepatic carcinoma cells and human umbilical vein endothelial cells.
- Author:
Liu-cheng YANG
1
;
Zong-hai HUANG
;
Heng KONG
;
Qiang LI
;
Fei CHEN
;
Jin-long YU
;
Zhou LI
Author Information
- Publication Type:Journal Article
- MeSH: Adenoviridae; genetics; Apoptosis; genetics; Cells, Cultured; Cytosine Deaminase; genetics; metabolism; Endothelial Cells; cytology; Genes, Transgenic, Suicide; genetics; Genetic Therapy; Genetic Vectors; Humans; Liver Neoplasms; pathology; Promoter Regions, Genetic; genetics; Recombinant Fusion Proteins; genetics; metabolism; Thymidine Kinase; genetics; metabolism; Tumor Cells, Cultured; Umbilical Veins; cytology; Vascular Endothelial Growth Factor Receptor-2; genetics; metabolism
- From: Journal of Southern Medical University 2009;29(1):1-4
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the selective killing effects of adenovirus (Ad)-mediated double suicide gene system driven by KDR promoter (KDR-CdglyTK) on the human hepatic carcinoma cells and human umbilical vein endothelial cells (HUVECs).
METHODSKDR-expressing BEL-7402 and HUVECs and HepG2 cells that did not express KDR were infected by KDR-CdglyTK, and the infection efficiency and the expression of CdglyTK in the cells was detected by RT-PCR. The infected cells were treated with the the prodrugs 5-FC and GCV at different concentrations, and the cell-killing effects and bystander effects were evaluated by MTT method.
RESULTSAt the multiplicity of infection (MOI) of 100, the recombinant AdKDR-CDglyTK showed similar infection efficiency in the 3 cell lines. RT-PCR demonstrated CDglyTK expression in the recombinant adenovirus and the 3 infected cell lines. BEL-7402 and HUVECs infected by the KDR-CdglyTK, but not the HepG2 cells, were highly sensitive to the prodrugs (P<0.001). Bystander effects of the double suicide gene system were observed in the coculture of the infected and non-infected BEL-7402 and HUVECs.
CONCLUSIONThe double suicide gene system driven by KDR promoter has specific killing effect on KDR-expressing hepatocellular carcinoma cells and HUVECs.
