Zhang Xiaoyuan,Zhu Xinhong,Lin Cunzhi,Wang Lijun,Sun Jiaxing,Li Haihong.Combination effect of oncolytic virus H101 and radiation on apoptosis induction and toxicity in A549 lung adenocarcinoma cells[J].Chinese Journal of Radiological Medicine and Protection,2017,37(9):656-660
Combination effect of oncolytic virus H101 and radiation on apoptosis induction and toxicity in A549 lung adenocarcinoma cells
Received:January 18, 2017  
DOI:10.3760/cma.j.issn.0254-5098.2017.09.003
KeyWords:Oncolytic virus  Lung adenocarcinoma cells  Apoptosis  Toxicity
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Author NameAffiliationE-mail
Zhang Xiaoyuan Departments of Respiratory Medicine, the Affiliated Hospital of Qingdao University, Qingdao 266003, China  
Zhu Xinhong Department of General Medicine, Qingdao Municipal Hospital, Qingdao 266071, China  
Lin Cunzhi Departments of Respiratory Medicine, the Affiliated Hospital of Qingdao University, Qingdao 266003, China lindoc@126.com 
Wang Lijun Departments of Respiratory Medicine, the Affiliated Hospital of Qingdao University, Qingdao 266003, China  
Sun Jiaxing Departments of Respiratory Medicine, the Affiliated Hospital of Qingdao University, Qingdao 266003, China  
Li Haihong Departments of Respiratory Medicine, the Affiliated Hospital of Qingdao University, Qingdao 266003, China  
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Abstract::
      Objective To investigate the apoptosis and toxicity of oncolytic virus H101 combined with radiation on apoptosis of A549 lung adenocarcinoma cells.Methods A549 lung adenocarcinoma cells in exponential growth phase were divided into four groups: control (PBS) group, radiation (IR) group, oncolytic virus (H101) group and radiation combined with oncolytic virus (IR+H101) group. The cells were double dyed with Annexin fluorescein isothiocyanate (V-FITC/PI) and then the apoptosis ratio of cells in every group was detected by the flow cytometry. The cytotoxic effect of cells in every group was detected by lactate dehydrogenase (LDH) release test. The mRNA expression of oncolytic viruses H101 capsid protein Hexon was detected by real-time fluorescence PCR (RT-PCR) to compare the oncolytic virus replication in each group.Results Cell apoptosis rate in H101 group (55.37%) was significantly higher than that in PBS group (1.03%) (t=36.51, P<0.05). Cell apoptosis rate in IR+H101 group (93.06%) was significantly higher than that in H101 group (55.37%), IR group (12.67%) and PBS group (1.03%) (t=13.51, 24.14, 38.99, P<0.05). LDH releasing percentage in IR group and H101 group at different time after virus transfection was significantly higher than that in PBS group (t=25.84, 39.38, 32.51, 78.18, P<0.05;t=31.40, 2.68, 23.43, 60.98, P<0.05). LDH releasing percentage in IR+H101 group was significantly higher than that in PBS group (t=80.71, 119.74, 109.80, 123.94, P<0.05), IR group (t=28.80, 54.34, 72.34, 61.91, P<0.05) and H101 group (t=42.02, 57.45, 57.01, 58.83, P<0.05). Compared with H101 group at the same time point, the mRNA expression of Hexon in IR+H101 group at 24, 48 and 72 h was increased by 16.26, 28.37 and 39.58 times, respectively (t=54.50, 33.73, 29.28, P<0.05).Conclusions The oncolytic virus H101 plays a role of radiosensitization in tumor cells. Radiation also increases the replication of the oncolytic virus H101 and thereby enhances the oncolytic effect of the oncolytic virus H101. Therefore, oncolytic virus H101 combined with radiotherapy has synergistic effect on killing tumor cells.
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