The purpose of this study is to determine whether an EBV-LMP1 targeted DNAzyme is effective in radiosensitization of nasopharyngeal carcinoma in combination with standard radiation therapy.

开始日期2009-05-01

申办/合作机构

中南大学湘雅三医院

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项与 DNAzyme targeting EBV-LMP1(Xiangya Hospital of Central South University) 相关的文献（医药）

2014-01-01·Cancer Biology & Therapy3区 · 医学

Targeting EBV-LMP1 DNAzyme enhances radiosensitivity of nasopharyngeal carcinoma cells by inhibiting telomerase activity

3区 · 医学

Article

作者: Xu, Zhijie ; Yang, Lifang ; Lu, Jingchen ; Sun, Lunquan ; Cao, Ya ; Liu, Liyu ; Luo, Xiangjian

The latent membrane protein 1 (LMP1), which is encoded by the Epstein-Barr virus (EBV), has been suggested to be one of the major oncogenic factors in nasopharyngeal carcinoma (NPC). In previous studies, we experimentally demonstrated that downregulation of LMP1 expression by targeting EBV-LMP1 DNAzyme (Dz1) could increase the radiosensitivity of NPC. However, how Dz1 contributes to the radiosensitivity in NPC is still not clear. In the present study, we confirmed that Dz1 decreases LMP1 expression and downregulates the expression of the catalytic subunit of telomerase (hTERT), both at the protein and mRNA levels (P<0.01), and therefore, consequently inhibits telomerase activity (P<0.05) in LMP1-positive NPC cells. We also observed that LMP1 mediated Akt phosphorylation is involved in the regulation of hTERT expression and phosphorylation. After LMP1 and hTERT expression was silenced by Dz1 and hTERT-targeted siRNA, respectively, the radiosensitivity increased in CNE1-LMP1 cells (P<0.05). The inhibition was more significant after Dz1 treatment was combined with siRNA (P<0.01). We concluded that hTERT expression and phosphorylation could be regulated by LMP1 through the Akt pathway, and Dz1 enhances radiosensitivity of LMP1-positive NPC cells by inhibiting telomerase activity.

2013-11-01·International Journal of Oncology2区 · 医学

EBV-LMP1-targeted DNAzyme induces DNA damage and causes cell cycle arrest in LMP1-positive nasopharyngeal carcinoma cells

2区 · 医学

Article

作者: Xingming Deng ; Lunquan Sun ; Min Tang ; Yiping Tang ; Ya Cao ; Jingchen Lu ; Xinxian Wen ; Zhijie Xu ; Lifang Yang ; Lanbo Xiao ; San Xu ; Xiaoqian Ma

This study aimed to determine the molecular mechanisms underlying the effect of the LMP1-targeted DNAzyme 1 (DZ1) on cell cycle progression in nasopharyngeal carcinoma (NPC) cells. We showed that the active DZ1 inhibited the expression of latent membrane protein 1 (LMP1) and induced a G1 phase arrest. In addition, this cell cycle deregulation was shown to be accompanied by upregulation of the DNA damage marker γ-H2AX, downregulation of the DNA damage response factor p-p53-Ser15 and cell proliferation inhibition. To investigate what affected the cell cycle progression, we examined the expression of two checkpoint-related cyclins and cyclin-dependent kinases (CDKs). We found a decrease of cyclin D1 and cyclin E protein levels at 24 h from the DZ1 treatment. Moreover, we observed inhibition of CDK4 activity and decreased cyclin D1 expression in the complexes immunoprecipitated with CDK4 antibody. We also found a reduction in cdc2 phosphorylation at Thr161 which partially stands for the cdc2 kinase activity in DZ1-treated CNE1-LMP1 cells, although the downregulation of LMP1 expression had no effect on the cyclin B1 and cdc2 expression. Further, we analyzed changes in cdc2 kinase activity induced by DZ1 and found that the downregulation of the LMP1 expression resulted in a 5-fold reduction in cdc2 kinase activity in CNE1-LMP1. The data suggest that the downregulation of the LMP1 expression by DZ1 was able to induce DNA damage, which then further inhibited the cell proliferation and resulted in malfunction of cell cycle checkpoints that led to G1 phase arrest and the decrease in number of cells in G2/M phase.

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