E1B55kDa缺失的增殖腺病毒抗肿瘤效果差异及其分子机制  

Antitumor efficacy and molecular mechanism of the E1B55kDa-deficient replicative adenovirus

作　　者：王伟国[1] 苏长青[2] 马炬明[1] 施建国[1] 胡慧珍[1] 李林芳[2] 姜梨华[2] 钱其军[2] 

机构地区：[1]解放军第117医院内科,杭州310004 [2]上海第二军医大学东方肝胆外科医院病毒与基因研究室,200438

出　　处：《临床肿瘤学杂志》2007年第11期801-804,共4页Chinese Clinical Oncology

基　　金：国家自然科学基金国际合作重大项目基金资助(30120160823);国家"863"高技术研究发展计划基金资助项目(2001AA217031)

摘　　要：目的:观察E1B55kDa缺失的增殖腺病毒CNHK200和CNHK200-hA对A549肺癌和MBD-231乳腺癌动物模型的抗肿瘤效果,结合研究肿瘤细胞柯萨奇病毒-腺病毒受体(CAR)的表达状态,分析腺病毒抗肿瘤效果的差别及其分子机制。方法:建立A549肺癌和MBD-231乳腺癌裸鼠模型,给予病毒总剂量1×109pfu的CNHK200和CNHK200-hA治疗。观察期结束,取肿瘤标本进行柯萨奇病毒-腺病毒受体(CAR)和腺病毒壳蛋白Hexon的免疫组化定位。结果:在CAR水平高表达的A549细胞内,CNHK200-hA和CNHK200均可以有效增殖并杀伤肿瘤细胞,产生明显的疗效。相反,在CAR水平低下的MBD-231细胞内,CNHK200-hA和CNHK200没有增殖复制能力,CNHK200几乎没有任何治疗效果,CNHK200-hA的治疗效果仅由Angiostatin基因表达所产生。结论:CAR在E1B55kDa缺失的增殖腺病毒的感染和增殖过程中起着至关重要的作用,肿瘤细胞CAR表达低下可以影响腺病毒载体的感染力和增殖力,从而降低用腺病毒进行肿瘤基因治疗的疗效。Objective：To observe the antitumor efficacy of the EIB55kDa-deficient replicative adenoviruses, CNHK200 and CNHK200-hA, on A549 and MBD-231 xenograft models, and analyze the difference of viral antitumor efficacy and their molecular mechanism combining the study of coxsackie-adenovirus receptor （ CAR ） expression. Methods： The A549 and MBD-231 xenograft models were established in nude mice, and treated with total 1 x 109 pfu of CNHK200-hA and CNHK200. After observation, CAR and adenoviral capsid hexon were detected by immunohistochemistry in tumor cells. Results： CNHK200-hA and CNHK200 could replicate in and lyse the CAR-overexpression A549 cells and yield the obvious antitumor effect in A549 xenograft models. But, they couldn＇t replicate in the CAR-negative MBD-231 ceils. CNHK200 had no efficacy in MBD-231 xenograft models, and the antitumor effect of CNHK200-hA was observed only by reason of angiostatin gene expression. Conclusion： CAR plays on important role in the infection and replication of E1B55kDa-deficient replicative adenoviruses. The low expression of CAR may influence the infection and replication of adenoviral vector, so that the efficacy of cancer gene therapy by adenoviruses is decreased.

关 键 词：增殖腺病毒 肿瘤模型 柯萨奇病毒-腺病毒受体 基因治疗 

分 类 号：R730.45[医药卫生—肿瘤]