Asialofetuin-hTERT-TK/GCV targeted gene therapy and its bystander effect on HepG2.
- Author:
Chang-qing YANG
1
;
Zhi-hua DENG
;
Yan LIU
;
Jing-long LIU
;
Yan CAO
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; Asialoglycoproteins; Bystander Effect; Fetuins; Ganciclovir; metabolism; Genes, Transgenic, Suicide; Genetic Therapy; Hep G2 Cells; Humans; Telomerase; metabolism; Thymidine Kinase; metabolism; Transfection; alpha-Fetoproteins
- From: Chinese Journal of Hepatology 2008;16(7):509-513
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo observe the targeted therapeutic effects of plasmid AF-pGL3-hTERT-TK on HepG2 cells.
METHODSHepG2 cells were cultured and pGL3-hTERT-TK and AF-liposome were constructed. HepG2 and L02 cells were transfected with AF-pGL3-hTERT-TK. The growth, apoptosis of the cells and the bystander effects were studied using liquid scintillation analysis and tunnel and flow cytometry.
RESULTSAfter the suicide gene was inserted into the downstream of hTERT, TK was effectively driven by the hTERT promoter, making the TK highly expressed in the HepG2 cells. The AF made the therapeutic gene enter the HepG2 cells more easily by recognizing and combining the ASGPR receptor protein on the HepG2 cell surfaces and induced their apoptosis and suicide with bystander effect. The apoptosis rate was 85%+/-3% in the HepG2 cells whereas in the normal L02 hepatic cells it was 16%+/-2%.
CONCLUSIONAF-pGL3-hTERT-TK can target and attack HepG2 cells and has almost no influence on normal L02 hepatic cells. AF-pGL3-hTERT-TK has a potential in the treatment of hepatocellular carcinomas.
