Target expression of Staphylococcus enterotoxin A from an oncolytic adenovirus suppresses mouse bladder tumor growth and recruits CD3+ T cell
Target expression of Staphylococcus enterotoxin A from an oncolytic adenovirus suppresses mouse bladder tumor growth and recruits CD3+ T cell
复制标题
DOI：
10.1007/s13277-013-0847-3
复制
发表时间：
2013-10-01
期刊：
影响因子：
--
通讯作者：
Wu, Yongping
中科院分区：
文献类型：
--
作者：
Han, Conghui;Hao, Lin;Wu, Yongping
我们最近设计了一种表达超抗原葡萄球菌肠毒素A(SEA)的溶瘤腺病毒(PPE3-SEA)，由于端粒酶逆转录酶和低氧诱导因子启动子分别调控E1A和E1B基因的表达，因此提高了肿瘤的特异性。在此，我们检测了PPE3-SEA重组腺病毒在体内外对小鼠膀胱癌MB49细胞增殖的抑制作用。PPE3-SEA感染体外培养的小鼠MB49细胞可引起细胞病变，RT-PCR和Western印迹法检测SEA基因和蛋白的表达。在同基因C57BL/6小鼠皮下建立了MB29膀胱肿瘤模型。10天后，瘤内注射溶瘤病毒或PBS。分别于治疗后第1、3、5、7、9、11天测量肿瘤大小，计算肿瘤体积。8只经PPE3-SEA治疗的小鼠中有1只在第9天时未见肿瘤。PPE3-SEA治疗组在治疗后第5天开始的平均肿瘤体积显著小于对照组(p<；0.01)，肿瘤内纤维组织增多，浸润性CD3+T细胞增多。PPE3-SEA处理组大鼠肝肾大体形态及组织学切片与对照组相似。综上所述，溶瘤腺病毒可以提供一种新型的将SEA运送到肿瘤部位的载体，PPE3-SEA作为一种潜在的抗膀胱癌药物值得进一步研究。
We recently engineered an oncolytic adenovirus (PPE3-SEA) that expresses the superantigen, Staphylococcus enterotoxin A (SEA), and that has enhanced tumor specificity because the telomerase reverse transcriptase and hypoxia-inducible factor promoters regulate expression of E1A and E1B genes, respectively. Here, we evaluated the PPE3-SEA adenovirus anti-tumor activity against MB49 mouse bladder cancer cell proliferation in vitro and in vivo. PPE3-SEA infection of murine MB49 cells in vitro induced cytopathic effects, and significant expression of SEA mRNA and protein, as measured by RT-PCR and western blot, respectively. Subcutaneous MB29 bladder tumors were established in syngeneic C57BL/6 mice. After 10 days, tumors were injected with either oncolytic virus or PBS. Tumor dimensions were measured on days 1, 3, 5, 7, 9, and 11 post-treatment and tumor volumes were calculated. One of eight PPE3-SEA-treated mice had no tumor by day 9. PPE3-SEA treated group had significantly lower mean tumor volume beginning on day 5 post-treatment (p < 0.01), more fibrous tissue in the tumor, and increased presence of infiltrating CD3+ T cells than those of the control group. Gross appearance and histologic sections from the livers and kidneys of the PPE3-SEA-treated group were similar to those of the control group. In conclusion, oncolytic adenoviruses can provide a novel delivery vehicle for SEA to tumor sites, and PPE3-SEA warrants further study as a potential anti-tumor agent for bladder cancer.