Targeted antitumor effect induced by hTERT promoter mediated ODC antisense adenovirus
Targeted antitumor effect induced by hTERT promoter mediated ODC antisense adenovirus
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hTERT启动子介导的ODC反义腺病毒诱导的靶向抗肿瘤作用
DOI：
10.1007/s11033-009-9908-5
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发表时间：
2010-10-01
影响因子：
2.8
通讯作者：
Wang, Xiu-Li
中科院分区：
文献类型：
--
作者：
Wang, Wei;Jin, Bin;Wang, Xiu-Li
多胺生物合成的第一关键酶鸟氨酸脱羧酶（ODC）在癌细胞中表达增加。我们利用腺病毒介导的反义ODC阻断了前列腺癌和结直肠癌等肿瘤细胞的多胺合成途径。这些研究表明，ODC反义表达可以抑制肿瘤细胞的生长。为了达到将靶向基因治疗应用于临床的目的，我们将由癌症特异性启动子（hTERT启动子；端粒酶逆转录酶启动子）驱动的反义ODC RNA克隆到腺病毒载体（rAd-CMV-GFP-hTERTp-ODC）中。用rAd-CMV-GFP- htertp - odc和对照载体rAd-CMV-GFP分别感染人癌细胞HepG2、Bel-7402、A549和正常细胞株HELF、LO2。荧光素酶活性测定hTERT启动子活性。采用细胞生长曲线分析、western blot分析、流式细胞术分析和Matrigel侵袭试验评估细胞生长特性和侵袭性。结果显示，与PBS或rAd-CMV-GFP处理的癌细胞相比，rAd-CMV-GFP- htertp -ODC对ODC的表达和细胞增殖有明显抑制作用，而对正常细胞无明显抑制作用。我们的研究为癌症靶向治疗提供了一种强大而安全的新治疗策略。
The expression of Ornithine decarboxylase (ODC) which is the first key enzyme of polyamine biosynthesis is increased in cancer cells. We had blocked the polyamine synthesis pathway using the adenoviral-mediated antisense ODC in some cancer cells such as prostate cancers and colorectal cancers. These researches demonstrated that ODC antisense expression could inhibit tumor cell growth. In order to reach the goal of applying the targeting gene therapy in clinical practice, we cloned the antisense ODC RNA which was driven by cancer specific promoter (hTERT promoter; telomerase reverse transcriptase promoter) into the adenovirus vector (rAd-CMV-GFP-hTERTp-ODC). Human cancer cell lines (HepG2, Bel-7402, A549) and normal cell lines (HELF, LO2) were infected separately with rAd-CMV-GFP-hTERTp-ODC as well as with control vector (rAd-CMV-GFP). Luciferase activity assay was performed to determine hTERT promoter activity. Cell growth curves analysis, western blot analysis, flow cytometry analysis and Matrigel invasion assays were performed to assess properties of cell growth and invasiveness. The results showed that there was significant inhibition of ODC expression and cell proliferation in cancer cells treated with rAd-CMV-GFP-hTERTp-ODC compared with cells treated with PBS or rAd-CMV-GFP, and no significant inhibition was detected in normal cells. Our research offers a powerful and safe new therapeutic strategy for cancer targeted treatment.