Influence of coxsackie-adenovirus receptor expression on infection efficiency of adenovirus vector in gene therapy of hepatocellular carcinoma
- VernacularTitle:CAR的表达调节对肝癌基因治疗中腺病毒载体感染效率的影响
- Author:
Yun WU
- Publication Type:Journal Article
- Keywords:
coxsackie-adenovirus receptor;
U0126;
adenovirus;
infection efficiency;
hepatocellular carcinoma;
gene therapy
- From:
Chinese Journal of Cancer Biotherapy
1995;0(03):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the relationship between coxsackie-adenovirus receptor(CAR)expression and the infection efficiency of adenovirus vector in gene therapy for hepatocellular carcinoma through regulating CAR expression on cells surface via inhibition of the Raf/MEK/ERK pathway.Methods: Western blotting analysis was used to examine CAR expression in hepatocellular carcinoma cells(SMMC-7721 and HepG_2)before and after treatment with U0126,inhibitor of Raf/MEK/ERK signal transduetion.SMMC-7721 and HepG_2 were infected by a non-replicating,E1 A-deleted adenovirus expressing EGFP(Ad-GFP).FACS was used to analyze the infection efficiency of Ad before and after U0126 treatment. Results: The expression of CAR on cell surface had an increasing tendency after treatment with U0126.FACS analysis showed significantly increased infectivity of cells treated with the MEK inhibitor U0126 compared with untreated cells: SMMC-7721,(71.65?6.21)%→(86.54?5.70)%,HepG_2,(77.53?4.62)%→(87.06?2.83)%,when infected with Ad-GFP at the same MOI(10 MOI).Conclusion: The inhibition of Raf/MEK/ERK pathway by U0126 may up-regulate the expression of CAR in some hepatocellular carcinoma cells,which subsequently enhances the susceptibility of adenovirus infection to target cells.