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Chinese Archives of General Surgery(Electronic Edition) ›› 2009, Vol. 03 ›› Issue (02): 12-14. doi: 10.3877/cma.j.issn.1674-0793.2009.02.004

• Original Articles • Previous Articles     Next Articles

Study of yeast CDglyTK double suicide gene driven by AFP promoter for treatment of hepatocellular carcinoma in vivo

Yun-peng HUA1,(), Jia-ming LAI1, Shao-qiang LI1, Yong WANG1, Ying WANG1, Bao-jin LI1, Bao-yi ZHU1   

  1. 1.Department of Hepatobiliary Surgery, the First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China
  • Received:2008-12-09 Online:2009-04-01 Published:2024-11-30
  • Contact: Yun-peng HUA

Abstract:

Objective

To study the effects and mechanisms of yeast cytosine deaminase/thymidine kinase (yCDglyTK)double suicide gene driven by alpha fetoprotein (AFP)promoter on hepatocellular carcinoma(HCC) in vivo.

Methods

To construct the expression plasmid with yCDglyTK double suicide gene driven by AFP promoter,HepG2 (AFP positive)and SMMC7721 (AFP negative)human HCC cell xenografts in nude mice were both transfected with the above-mentioned expression plasmid through cationic liposome,followed by treatment of the prodrugs 5-fluorocytosine (5-FC) and/or ganciclovir (GCV). The effect of inhibition was observed through measuring the tumor size and the number of apoptosis cells.

Results

The double suicide gene was expressed selectively on HepG2 cell xenografts, rather than on SMMC7721 cells. The prodrugs 5-FC and/or GCV could inhibit effectively the growth of HepG2 cell xenografts,but had no influence on SMMC7721 cells. The inhibitive effects of different prodrugs on HepG2 cells were GCV+5-FC>5-FC>GCV.Apoptotic cells were found in HepG2 xenografts after the treatment of prodrugs. However, in SMMC7721 cell xenografts, few apoptotic cells were found.

Conclusions

yCDglyTK double suicide gene driven by AFP promoter has a significant efficacy in treatmentof AFP positive HCC.Cell apoptosis may be an important mechanism of inhibiting the growth ofHCC.

Key words: Carcinoma,hepatocelluar, Genetherapy, Genes,transgenic,suicide

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