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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2014, Vol. 34 Issue (1): 15-20    DOI: 10.13523/j.cb.20140103
研究报告     
癌症靶向基因-病毒ZD55-XAF1抗肝癌移植瘤的生长及其安全性研究
马步云, 何婉婉, 周立, 王毅刚
浙江理工大学生命科学学院 新元医学与生物技术研究所 杭州 310018
The Study on Anticancer Effect of Targeting Gene-Virus ZD55-XAF1 in Liver Cancer Xenograft of Mice and Its Safety
MA Bu-yun, HE Wan-wan, ZHOU Li, WANG Yi-gang
Xinyuan Institute of Medicine and Biotechnology, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China
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摘要： 目的：探讨溶瘤腺病毒（ZD55-gene）作为载体携带外源抗癌基因（XAF1）抗肝癌移植瘤的生长及其安全性。方法：抽提溶瘤腺病毒ZD55-XAF1的基因组DNA，PCR扩增鉴定病毒；细菌平板培养和支原体检测试剂盒检测细胞有无细菌、支原体污染；通过荷瘤小鼠动物实验，观察溶瘤腺病毒ZD55-XAF1对肝癌移植瘤生长的抑制、小鼠的临床反应指标、血清肝毒性指标、各脏器组织中的病毒残留分布及病理切片观察。结果：细胞培养过程无细菌和支原体污染；较对照组，受试小鼠血清肝酶AST活性上升（P<0.05），而ALT和ALP活性基本无变化（P>0.05）；PCR检测各脏器均有病毒基因组DNA存在；HE染色显示受试小鼠各脏器具有不同程度的损伤，病毒处理对肿瘤细胞具有明显的杀伤效果，而受试小鼠的临床反应并无明显异常。结论：溶瘤腺病毒ZD55-XAF1能够抑制肿瘤生长，杀死肿瘤细胞，对小鼠血清肝酶活性影响较小而对各脏器有不同程度的轻微损伤，作为癌症基因治疗载体有潜在的应用价值但其安全性还有待提高。
关键词： 溶瘤腺病毒;  基因治疗载体;  安全性    
Abstract: Purpose:To investigate the safety in oncolytic adenovirus (ZD55-gene) as a vector,introducing antitumor gene (XAF1) at the process of cancer therapy. Methods:Genomic DNA of oncolytic adenovirus ZD55-XAF1 was extracted and PCR was used to identify the ZD55-XAF1;To measure the bacteria and mycoplasma contamination during cell culture, supernatant was cultivated in LB solid medium and mycoplasma was tested by detection kits; After intravenous injection of ZD55-XAF1, several indicators were evaluated, including antitumor activity of ZD55-XAF1,clinical responses of the mice, levels of serum enzymes ALT, AST and ALP, residual and distribution of the virus in tissues,HE staining of various organs. Results:No contamination was found during cell culture,which were used for virus amplification. Except the AST,the levels of serum enzymes were normal(P>0.05). Residual and distribution of the virus in tissue stayed normal. But HE staining showed damage on mice organs and tumor was suppressed. Conclusion:Oncolytic adenovirus ZD55-XAF1 can effectively suppress tumor growth and viability of tumor cells with little impact on serum enzymes.But hematoxylin and eosin (HE)staining showed different degrees of damage on mice organs. Oncolytic adenovirus as a vector for cancer gene therapy has potential applied value but its safety needs to be improved.
Key words: Oncolytic adenovirus    Gene therapy    Safety
收稿日期: 2013-11-14 出版日期: 2014-01-25
ZTFLH:  Q813  
基金资助: 国家自然科学基金（81272687）；浙江省自然科学基金（Z13H160020）资助项目
通讯作者: 王毅刚，E-mail：wangyigang43@163.com     E-mail: wangyigang43@163.com
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引用本文:

马步云, 何婉婉, 周立, 王毅刚. 癌症靶向基因-病毒ZD55-XAF1抗肝癌移植瘤的生长及其安全性研究[J]. 中国生物工程杂志, 2014, 34(1): 15-20.

MA Bu-yun, HE Wan-wan, ZHOU Li, WANG Yi-gang. The Study on Anticancer Effect of Targeting Gene-Virus ZD55-XAF1 in Liver Cancer Xenograft of Mice and Its Safety. China Biotechnology, 2014, 34(1): 15-20.

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https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20140103    或    https://manu60.magtech.com.cn/biotech/CN/Y2014/V34/I1/15

[1] Bauzon M, Hermiston T W. Exploiting diversity: genetic approaches to creating highly potent and efficacious oncolytic viruses. Current opinion in molecular therapeutics, 2008, 10 (4): 350-355.
[2] Gil Z, Rein A, Brader P, et al. Nerve-sparing therapy with oncolytic herpes virus for cancers with neural invasion. Clinical Cancer Research, 2007, 13(21): 6479-6485.
[3] Jounaidi Y, Doloff J C, Waxman D J. Conditionally replicating adenoviruses for cancer treatment. Current Cancer Drug Targets, 2007, 7(3): 285-301.
[4] Tai C K, Kasahara N. Replication-competent retrovirus vectors for cancer gene therapy. Front Biosci, 2008, 13: 3083-3095.
[5] Zhang Q, Yong A Y, Wang E, et al. Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus. Cancer research, 2007, 67(20): 10038-10046.
[6] 陈霜凝, 沈园园, 黄文林, 等.抗肿瘤腺病毒纳米复合物的研究进展.中国新药杂志, 2012, 21(4):378-384. Chen SH N, Shen Y Y, Huang W L, et al.Advaneces in research on adenovirus nanocomplexes for tumor therapy.Chinese Journal of New Drugs, 2012, 21(4);378-384.
[7] 刘新垣. 一种抗癌新策略——肿瘤的基因病毒治疗. 中国肿瘤生物治疗杂志, 2001, 8(1): 1. Liu X Y.A novel anticancer strategy——gene-viro therapy in tumor.Chinese Journal of Cancer Biotherapy, 2001, 8(1):1.
[8] Liu X Y. Targeting gene-virotherapy of cancer and its prosperity. Cell Res 2006; 16(11): 879-886.
[9] Liston P, Fong W G, Kelly N L, et al. Identification of XAF1 as an antagonist of XIAP anti-caspase activity. Nature Cell Biology, 2001, 3(2): 128-133.
[10] Qi R, Gu J, Zhang Z, et al. Potent antitumor efficacy of XAF1 delivered by conditionally replicative adenovirus vector via caspase-independent apoptosis. Cancer Gene Therapy, 2007, 14(1): 82-90.
[11] Arora V, Cheung H H, Plenchette S, et al. Degradation of survivin by the X-linked inhibitor of apoptosis (XIAP)-XAF1 complex. Journal of Biological Chemistry, 2007, 282(36): 26202-26209.
[12] Qiao L, Gu Q, Dai Y, et al. XIAP-associated factor 1 (XAF1) suppresses angiogenesis in mouse endothelial cells. Tumor Biology, 2008, 29(2): 122-129.
[13] 何婉婉, 周立, 刘涛, 等.溶瘤腺病毒作为癌症基因治疗载体的研究进展及安全性评价.中国细胞生物学学报, 2013, 35(9):1386-1391. He W W, Zhou L, Liu T et al.Oncolytic adenovirus as a vector of gene therapy for cancer progression and safety evaluation. Chinese Journal of Cell Biology, 2013, 35(9):1386-1391.
[14] Nemunaitis J, Khuri F, Ganly I, et al. Phase Ⅱ trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer. Journal of Clinical Oncology, 2001, 19(2): 289-298.
[15] 胡奇婵, 陈玥, 王丽, 等. 腺病毒载体用于基因治疗的研究进展. 解放军医药杂志, 2011, 23(5): 76-80. Hu Q C, Chen Y, Wang L, et al.Medical & Pharmaceutical Journal of Chinese People's Liberation Army, 2011, 23(5):76-80.
[16] Yu W, Fang H. Clinical trials with oncolytic adenovirus in China. Current Cancer Drug Targets, 2007, 7(2): 141-148.
[17] Russell S J, Peng K W, Bell J C. Oncolytic virotherapy. Nature Biotechnology, 2012, 30(7): 658-670.
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