Effect of combined treatment of radiation and tissue-specific recombinant oncolytic adenovirus on bladder cancer cells
Effect of combined treatment of radiation and tissue-specific recombinant oncolytic adenovirus on bladder cancer cells
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放射与组织特异性重组溶瘤腺病毒联合治疗对膀胱癌细胞的影响
DOI：
10.1080/09553002.2017.1231942
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发表时间：
2017-02
影响因子：
2.6
通讯作者：
Wang Zhiping
中科院分区：
文献类型：
--
作者：
Zhang Hongjuan;Wang Fang;Mao Chunjie;Zhang Zuncheng;Fu Shengjun;Lu Jianzhong;Zhai Zhenxing;Li Renju;Li Shuwen;Rodriguez Ron;Wang Zhiping
摘要目的：基因治疗结合放射治疗肿瘤已显示出良好的潜力。本研究旨在阐明放射治疗联合膀胱癌组织特异性溶瘤腺病毒（Ad-PSCAE-UPII-E1 A）对膀胱癌细胞的协同作用，并探讨其协同作用机制。材料与方法：成功构建了携带UPII启动子和前列腺干细胞抗原增强子（PSCAE）调控下的E1 A腺病毒。MTT法测定膀胱癌细胞BIU-87和EJ的存活率。流式细胞术和透射电镜观察细胞凋亡。通过TCID 50测定病毒滴度，并通过Western印迹法分析蛋白Mre 11、Chk 2-Thr 68和E1 A。结果如下：溶瘤腺病毒联合放射治疗与单次治疗相比，提高了抗肿瘤疗效，并具有X线剂量依赖性。当腺病毒感染计划在照射后24小时，癌细胞的活力最低。腺病毒和辐射通过caspase-3相关的凋亡途径诱导细胞死亡，并且膀胱癌细胞被阻滞在G1期（BIU-87）或S期（EJ）。放射线和腺病毒处理后的膀胱癌细胞内出现自噬空泡。照射后，在BIU-87和EJ细胞中观察到更多的病毒颗粒。然而，通过TCID 50测定，辐照的膀胱癌细胞和未辐照的细胞之间的病毒滴度没有差异。照射后溶瘤腺病毒中参与DNA断裂修复的蛋白Mre 11、Chk 2-Thr 68减少，γ-H2 AX-Ser 139增加，E1 A基因和六邻体蛋白增加。结论：本研究结果表明腺病毒Ad-PSCAE-UPII-E1 A与放射线联合应用具有协同抗肿瘤作用，可能成为膀胱癌治疗的一种新策略。
Abstract Purpose: Gene therapy combined with radiation has shown promising potential for the treatment of tumors. This paper aimed to clarify the synergistic effect of radiotherapy combined with the bladder cancer tissue-specific oncolytic adenovirus (Ad-PSCAE-UPII-E1A) on bladder cancer cells and to study the underlying synergy mechanisms of the combined treatment. Materials and methods: The Adenovirus carrying E1A under control of UPII promoter and prostate stem cell antigen enhancer (PSCAE) were successfully constructed. The viability of bladder cancer cells BIU-87 and EJ was determined by MTT assay. The apoptotic assay was demonstrated by flow cytometry and TEM. Virus titer was determined by TCID50 assay, and proteins Mre11, Chk2-Thr68, and E1A were analyzed by Western blot method. Results: Oncolytic adenovirus combined with radiotherapy improved antitumor efficacy compared with the single treatment at a time and was X-ray dosage-dependent. When the adenovirus infection was scheduled at 24 h after irradiation, cancer cells had the lowest viability. Adenovirus and irradiation induced cell death through the caspase-3 related apoptotic pathway, and bladder cancer cells were arrested at the G1 (BIU-87) or S phase (EJ). Autophagic vacuoles were observed in bladder cancer cells treated with radiation and adenovirus. After irradiation, more virus particles were observed in the BIU-87 and EJ cells. However, by a TCID50 assay, there was no difference in virus titter between irradiated bladder cancer cells and unirradiated cells. The proteins Mre11, Chk2-Thr68 which involved in the DNA break repair pathway were decreased while γ-H2AX-Ser139 increased; at the same time, the E1A gene and the hexon proteins of oncolytic adenovirus were increased after irradiation. Conclusions: Our results proved synergistic antitumor effect of adenovirus Ad-PSCAE-UPII-E1A and radiation, which might be a potential therapeutic strategy for bladder cancer.
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影响因子：
6.4
作者：
Dilley, J;Reddy, S;Yu, DC
通讯作者：
Yu, DC
影响因子：
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