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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 effect of CNHK200 and CNHK200-hA, which are absent of E1B55kDa, on the animal models of A549 lung cancer and MBD-231 breast cancer. Combined with the study of the expression status of Coxsackievirus Adenovirus Receptor (CAR) Analysis of adenovirus antineoplastic effects of the difference and its molecular mechanisms. METHODS: A549 lung cancer and MBD-231 breast cancer nude mice model were established and treated with CNHK200 and CNHK200-hA at a total dose of 1 × 109pfu. At the end of the observation period, the tumor samples were taken for immunohistochemical localization of Coxsackie virus-adenovirus receptor (CAR) and adenovirus capsid protein Hexon. Results: In A549 cells with high CAR level, both CNHK200-hA and CNHK200 could effectively proliferate and kill tumor cells, with obvious curative effect. In contrast, CNHK200-hA and CNHK200 had no proliferative and replication abilities in low-CAR level MBD-231 cells, CNHK200 had almost no therapeutic effect, and the therapeutic effect of CNHK200-hA was only caused by Angiostatin gene expression. CONCLUSION: CAR plays a crucial role in the process of infection and proliferation of adenovirus deleted E1B55kDa. The low expression of CAR in tumor cells can affect the infectivity and proliferative capacity of adenovirus vector and thus reduce the use of adenovirus for tumor gene therapy Efficacy.