Targeting gene therapy for hepatocarcinoma cells with the E. coli purine nucleoside phosphorylase suicide gene system directed by a chimeric α-fetoprotein promoter
Targeting gene therapy for hepatocarcinoma cells with the E. coli purine nucleoside phosphorylase suicide gene system directed by a chimeric α-fetoprotein promoter
复制标题
DOI：
10.1016/j.canlet.2008.01.027
复制
发表时间：
2008-06-08
期刊：
影响因子：
9.7
通讯作者：
Lin, Junsheng
中科院分区：
文献类型：
--
作者：
Cai, Xiaokun;Zhou, Junli;Lin, Junsheng
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-beta-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 alpha-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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
