Over-expression of human TERT C-terminal polypeptide driven by Egr-1 promoter enhances 5-FU induced nasopharyngeal carcinoma growth inhibition and apoptosis
hTERTC27,a 27 kDa C-terminal polypeptide,can induce telomere dysfunction and inhibit tumor cell proliferation.To study the synergistic anti-tumor effects of hTERTC27 polypeptide driven by Egr-1 promoter and chemotherapeutics 5-flurorouracil (5-FU) on nasopharyngeal carcinoma (NPC),hTERTC27 eDNA was constructed to the downstream of the Egr-1 promoter,and 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 5-FU activated Egr-1 promoter in C666-1 cells.Over expressed hTERTC27 made the cells more sensitive to 5-FU,and additionally inhibited cell proliferation about 20.41%.Combinational therapy of over expressed hTERTC27 driven by 5-FU activated Egr-1 promoter and 5-FU synergistically inhibited cell proliferation and promoted apoptosis of C666-1 cells for about 4.75 folds and 1.76 folds in comparison with sole therapy of hTERTC27 or 5-FU in vitro.In vivo experiments showed that over expressed 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 over expressed hTERTC27,which is driven by 5-FU activated Egr-1 promoter,and 5-FU may provide a novel approach to treat nasopharyngeal cancer.
Egr-1 hTERTC27 5-FU Nasopharyngeal carcinoma gene therapy
Guimiao Lin Wenqi Jiang Marie C.M.Lin Suxia Lin Hong Yao Wanxian Yi Samuel S.M.Ng Xiaomei Wang
School of Medical Sciences,Shenzhen University,Shenzhen,518060,China BrainTumor Centre,Division of Neurosurgery,Department of Surgery,The Chinese University of Hongkong,
国内会议
2012医学科学前沿暨第二届个体化治疗与抗肿瘤药物研究新趋向研讨会
深圳
英文
90-107
2012-07-13(万方平台首次上网日期,不代表论文的发表时间)