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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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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.
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Received: 14 November 2013
Published: 25 January 2014
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[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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