Targeting gene therapy for hepatocarcinoma cells with the E. coli purine nucleoside phosphorylase suicide gene system directed by a chimeric α-fetoprotein promoter
- 作者：Xiaokun Cai ; Junli Zhou ; Ying Chang ; Xuemei Sun ; Peiyuan Li ; Junsheng Lin
- 关键词：Hepatocarcinoma (HCC) ; Targeting gene therapy ; Purine nucleoside phosphorylase (PNP) suicide gene ; Chimeric
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- 刊名：Cancer Letters
- 出版年：2008
- 期刊代码：44_03043835
- 类别：med
- 出版时间：8 June 2008
- 卷：264
- 期：1
- 页码：71-82
- 文件大小：1327 K
摘要
For hepatocarcinoma (HCC) gene therapy, the tumoricidal efficacy and selective expression of therapeutic gene remain two major challenges. The Escherichia coli (E. coli) purine nucleoside phosphorylase (PNP)/9-(2-deoxy-β-dribofuranosyl)-6-methylpurine (MeP-dR) suicide gene system exhibits excellent anti-tumor effects, indicating this system directed by a HCC-specific promoter would offer a possibility of targeting gene therapy for HCC. To test this hypothesis, here, we prepared a plasmid (p[HRE]AF/PNP) containing the E. coli PNP/MeP-dR system and a chimeric human 
-fetoprotein (AFP) promoter, [HRE]AF. We introduced this plasmid into AFP-positive and low-AFP-generating human HCC cells, and evaluated its therapeutic effects on both human HCC cell lines. In the presence of hypoxia, the E. coli PNP gene directed by the [HRE]AF promoter were HCC-specifically expressed in two human HCC cell lines and, moreover, the [HRE]AF-PNP/MeP-dR therapy would yield significant and selective cytotoxicity in both AFP-positive and low-AFP-generating HCC cells. Our findings suggest the [HRE]AF-PNP/MeP-dR therapy has worthy potentialities as an effective strategy for targeting therapy of AFP-positive, and especially AFP-negative or low-AFP-generating HCC.
-fetoprotein (AFP) promoter, [HRE]AF. We introduced this plasmid into AFP-positive and low-AFP-generating human HCC cells, and evaluated its therapeutic effects on both human HCC cell lines. In the presence of hypoxia, the E. coli PNP gene directed by the [HRE]AF promoter were HCC-specifically expressed in two human HCC cell lines and, moreover, the [HRE]AF-PNP/MeP-dR therapy would yield significant and selective cytotoxicity in both AFP-positive and low-AFP-generating HCC cells. Our findings suggest the [HRE]AF-PNP/MeP-dR therapy has worthy potentialities as an effective strategy for targeting therapy of AFP-positive, and especially AFP-negative or low-AFP-generating HCC.