Abstract:Objective: To explore the effects of recombinant avirulent newcastle disease virus LaSota strain expressing the rabies virus glycoprotein (rl-RVG) on the proliferation of A549 lung adenocarcinoma tumor-bearing mice and potential immune mechanism. Methods: A tumor model of human A549 into nude mice was constructed and divided randomly into rl-RVG group, newcastle disease virus(NDV) group and control group. The mice in each group received rlRVG, NDV and PBS injection, respectively, twice a week, for 3 weeks. The growth of tumor were recorded, and the expression of NDV and rabies virus glycoprotein (RVG) were assayed by immunohistochemistry. The pathological change of the tissues were observed by HE staining. The number of NK (CD3-CD49+) cells were detected by flow cytometry. Results: Compared with the control group, the growth of tumor in rl-RVG group and NDV group were inhibited more effectively. The subcutaneous tumor necrosis were more evident and there were much more multinucleated giant cells in the spleen tissue of the mice in rlRVG group and NDV group. Immunohistochemical analysis showed that RVG protein was expressed in rl-RVG group and NDV protein was expressed in both rl-RVG group and NDV group. The number of NK cells was significantly higher in rl-RVG group and NDV group than that in the control group, and in rl-RVG group it was more higher than that in NDV group. Conclusion: Recombinant rl-RVG transfected successfully, and effectively inhibited the growth of A549 lung adenocarcinoma by mechanism which activating cell immune response.
\[1\]张琪,杨呜琦,王根辈,等. 新城疫病毒和康莱特注射液联合抗肿瘤试验中瘤组织的病理变化及IL6表达的研究\[J\]. 中国兽医杂志, 2010, 46(10):33-34.\[2\]王亚君,宋纯,李晓辉,等. 新城疫病毒抗人急性单核细胞白血病作用的实验研究\[J\]. 中国当代儿科杂志, 2011, 13(2):149-152.\[3\]宫金伶,黄川,宋德志,等. 新城疫病毒7793株对人结肠癌细胞的杀伤作用\[J\]. 现代肿瘤医学, 2011, 19(3):414-417.\[4\]Bukreyev A, Huang Z, Yang L, et al. Recombinant newcastle disease virus expressing a foreign viral antigen is attenuated and highly immunogenic in primates\[J\]. J Virol, 2005, 79 (21):13275-13284.\[5\]DiNapoli JM, Kotelkin A, Yang L, et al. Newcastle disease virus, a host rangerestricted virus, as a vaccine vector for intranasal immunization against emerging pathogens\[J\]. Proc Natl Acad Sci U S A, 2007, 104(23):9788-9793.\[6\]DiNapoli JM, Nayak B, Yang L, et al. Newcastle disease virusvectored vaccines expressing the hemagglutinin or neuraminidase protein of H5N1 highly pathogenic avian influenza virus protect against virus challenge in monkeys\[J\]. J Virol, 2010, 84(3):1489-1503.\[7\]Inoue Ki, Shoji Y, Kurane I, et al. An improved method for recovering rabies virus from cloned cDNA\[J\]. J Virol Methods, 2003, 107(2):229-236.\[8\]Pr haud C, Lay S, Dietzschold B, et al. Glycoprotein of nonpathogenic rabies virus is a key determinant of human cell apoptosis\[J\]. J Virol, 2003, 77(19):10537-10547.\[9\]McGinners LW, Morrison TG. Modulation of the activities of HN protein of Newcastle disease virus by nonconserved cystein residues\[J\]. Virus Res, 1994, 34(3):305-316.\[10\]Wheelock EF, Dingle JH. Observations on the repeated administration of viruses to a patient with acute leukaemia. A preliminary report\[J\]. N Engl J Med, 1964, 271:645-651.\[11\]Elankumaran S, Rockemann D, Samal SK. Newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death\[J\]. J Virol, 2006, 80(15):7522-7534.\[12\]Hrabk A, Csuka I, Bajor T, et al. The cytotoxic antitumor effect of MTH-68/H, a live attenuated Newcastle disease virus is mediated by the induction of nitric oxide synthesis in rat peritoneal macrophages in vitro\[J\]. Cancer Lett, 2006, 231(2):279-289.\[13\]Bian H, Fournier P, Peeters B, et al. Tumortargeted gene transfer in vivo via recombinant Newcastle disease virus modified by a bispecific fusion protein\[J\]. Int J Oncol, 2005, 27(2):377-384.\[14\]Cassel WA, Murray DR. Treatment of stageⅡmalignant melanoma patients with a Newcastle disease virus oncolysate\[J\]. Nat Immun Cell Growth Regul, 1988, 7(5/6):351-352.\[15\]Johnson N, Letshwenyo M, Baipoledi EK, et al. Molecular epidemiology of rabies on Botswana:a comparison between antibody typing and nucleotide sequence phylogeny\[J\]. Vet Microbiol, 2004, 101(1):31-38.\[16\]李银聚,吴庭才. 鸡新城疫病毒抗人肿瘤性疾病的分子机制\[J\]. 生物学通报, 2009, 44(6):13-14.\[17\]Zeng J, Fournier P, Schirrmacher V. Induction of interferonα and tumor necrosis factor-related apoptosis-inducing ligand in human blood mononuclear cells by hemagglutininneuraminidase but not F protein of Newcastle disease virus\[J\]. Virology, 2002, 297(1):19-30.\[18\]Ge J, Wang X, Tao L, et al. Newcastle disease virusvectored rabies vaccine is safe, highly immunogenic, and provides long-lasting protection in dogs and cats\[J\]. J Virol, 2011, 85(16):8241-8252.\[19\]Dietzschold B, Schnell M, Koprowski H. Pathogenesis of rabies\[J\]. Curr Top Microbiol Immunol, 2005, 292:45-56.\[20\]白莲花,钱振超,于春,等. 新城鸡瘟病毒激活的巨噬细胞抗肿瘤转移作用的研究\[J\]. 上海免疫学杂志, 1994, 14(6):334-336.