Early growth response protein-1 promoter-mediated synergistic antitumor effect of hTERTC27 gene therapy and 5-Flurorouracil on nasopharyngeal carcinoma.
Early growth response protein-1 promoter-mediated synergistic antitumor effect of hTERTC27 gene therapy and 5-Flurorouracil on nasopharyngeal carcinoma.
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DOI：
10.1089/cbr.2011.1153
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发表时间：
2012-09
影响因子：
3.4
通讯作者：
Guimiao Lin;Marie C. M. Lin;Suxia Lin;H. Yao;Shui-Qing Yu;Wanxian Yi;Gaixia Xu;S. Ng;Siping Chen;Jing Yu;Xiaomei Wang;Baoxue Yang
中科院分区：
文献类型：
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作者：
Guimiao Lin;Marie C. M. Lin;Suxia Lin;H. Yao;Shui-Qing Yu;Wanxian Yi;Gaixia Xu;S. Ng;Siping Chen;Jing Yu;Xiaomei Wang;Baoxue Yang
hTERTC 27是一种新构建的能诱导端粒功能障碍的多肽。为了研究早期生长反应蛋白-1（Egr-1）启动子驱动的hTERTC 27多肽与化疗药物5-氟尿嘧啶（5-FU）对鼻咽癌的协同抗肿瘤作用，进行了一系列体内外实验。结果表明，在C666-1细胞中，5-FU激活的Egr-1启动子使hTERTC 27的表达显著增加，最高达7.21倍。hTERTC 27的过表达使细胞对5-FU敏感性增加，并抑制细胞增殖20.41%。在体外，由5-FU激活的Egr-1启动子驱动的过表达的hTERTC 27与5-FU的联合治疗协同抑制C666-1细胞的增殖并促进细胞凋亡，与单独的hTERTC 27或5-FU治疗相比，分别约为4.75倍和1.76倍。体内实验表明，由5-FU激活的Egr-1启动子驱动的过表达的hTERTC 27与5-FU协同减少肿瘤体积、肿瘤重量和局部浸润，这可能与肿瘤细胞凋亡有关。这些结果表明，过表达的hTERTC 27，这是由5-FU激活的Egr-1启动子驱动，5-FU的联合治疗可能提供一种新的方法来治疗鼻咽癌。
hTERTC27 is a newly constructed polypeptide that can induce telomere dysfunction. To study the synergistic antitumor effects of the hTERTC27 polypeptide driven by the early growth response protein-1 (Egr-1) promoter and chemotherapeutic 5-flurorouracil (5-FU) on nasopharyngeal carcinoma, a series of in vitro and in vivo experiments were performed. The results showed that hTERTC27 expression was significantly increased up to 7.21-folds by the 5-FU-activated Egr-1 promoter in C666-1 cells. Overexpressed hTERTC27 made the cells more sensitive to 5-FU, and additionally, inhibited cell proliferation about 20.41%. Combinational therapy of overexpressed hTERTC27 driven by the 5-FU-activated Egr-1 promoter and 5-FU synergistically inhibited cell proliferation and promoted apoptosis of C666-1 cells for about 4.75-fold and 1.76-fold in comparison with a sole therapy of hTERTC27 or 5-FU in vitro. In vivo experiments showed that overexpressed hTERTC27 driven by 5-FU-activated Egr-1 promoter and 5-FU synergistically reduced tumor volume, tumor weight, and local infiltration, which may be relative to tumor cell apoptosis. These results suggest that combinational therapy of overexpressed hTERTC27, which is driven by the 5-FU-activated Egr-1 promoter, and 5-FU may provide a novel approach to treat nasopharyngeal cancer.