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
Yun-peng HUA, Jia-ming LAI, Shao-qiang LI, Yong WANG, Ying WANG, Bao-jin LI, Bao-yi ZHU. Study of yeast CDglyTK double suicide gene driven by AFP promoter for treatment of hepatocellular carcinoma in vivo[J]. Chinese Archives of General Surgery(Electronic Edition), 2009, 03(02): 12-14.