Gene therapy targeted to telomerase in HCC by AF-hTERT-TK/GCV

• Published in: The Chinese-German journal of clinical oncology Vol. 8; no. 7; pp. 415 - 419
• Main Authors: Deng, Zhihua, Yang, Changqing, Wang, Guiqin, Guo, Suya, Liu, Yan, Jia, Jing, Zhao, Jie
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 2009
• Subjects: Cancer Research; HCC; HepG2细胞; Medicine; Medicine & Public Health; Oncology; Surgical Oncology; 基因疗法; 治疗效果; 端粒酶; 肝癌细胞; 自动对焦; 荧光素酶; HCC; suicide gene TK; target gene therapy; h-TERT promoter; AF
• ISSN: 1610-1979; 1613-9089
• DOI: 10.1007/s10330-009-0036-4

Objective： The aim of this study was to observe the affection of targeted therapy to plasmid AF-pGL3-hTERT-TK in HCC cell line HepG2. Methods： We constructed therapeutic plasmid pGL3-hTERT-TK （containing suicide gene TK that promoted by promoter of hTERT） and was conjugated with AF-liposome （a protein that can combine with the receptor ASPGR on HCC cell surface）. Then we transfected HCC cell line HepG2 and hepatic cell L02 with AF-pGL3-hTERT-TK, observed the effects of therapeutic plasmid AF-pGL3-hTERT-TK for HCC cell line growth and apoptosis in vitro by Flow cytometry and Tun- nel method. Results： Our results showed that TK gene was 1100 bp in plasmid pGL3-hTERT-TK. Plasmid pGL3-hTERT-TK can effectively transfect HCC cell HepG2 and the transfection rate was 8.91%. By recognizing and combining effects of recep- tor protein ASPGR on HCC cell surface the therapeutic plasmid AF-pGL3-hTERT-TK could easily enter into HCC cell HepG2 and induce its apeptosis. The apoptosis rate was 85.87% while only 8.65% in L02 cell. Four days after AF-pGL3-hTERT-TK transfected HepG2 was intervention by ganciclovir （GCV）, a lot of apeptotic bodies were found by Tunnel analysis, while little apoptotic body was found in hepatic cell L02. Conclusion： AF-pGL3-hTERT-TK can target to HCC cell line and induce it to apoptesis, almost has no influence on hepatic cell L02. AF-pGL3-hTERT-TK has the potential therapeutic effects for HCC.