Virus-targeted therapy for tumors can effectively prolong the survival rate of patients and has become a new trend for cancer biotherapy. Oncolytic adenovirus (OAd) can specifically replicate in tumor cells, allowing the therapeutic genes carried to be rapidly copied. As known, solid tumors are always hypoxic, and researchers often overlook a key point, the replication of OAd depends not only on its own activity but also on the cellular hypoxic environment in which the virus replicates. In this study, we constructed an OAd carrying Decorin, HRE-Ki67-Decorin, combining the Ki67 promoter upstreamed with hypoxia-response element (HRE) sequences to drive adenoviral E1A. The OAd HRE-Ki67-Decorin had better replication ability under hypoxic conditions, downregulated cellular immunosuppressed growth factor TGF-β. In addition, HRE-Ki67-Decorin was potent in suppressing tumor growth and participated in the assembly of tumor extracellular matrix by expressing Decorin in subcutaneous renal cancer cell tumor models. Tumor sections from HRE-Ki67-Decorin-treated tissues had less collagen fibers and more spread of virus among tumor tissues. These results indicated that chimeric HRE-Ki67 promoter-regulated OAd carrying Decorin might be an effective anticancer treatment strategy.

中文翻译：

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由嵌合启动子驱动并带有核心蛋白聚糖的溶瘤腺病毒对抗肾细胞癌的功效。

肿瘤病毒靶向治疗可有效延长患者的生存率，已成为肿瘤生物治疗的新趋势。溶瘤腺病毒（OAd）可以在肿瘤细胞中特异性复制，使携带的治疗基因被快速复制。众所周知，实体瘤总是缺氧的，研究人员经常忽略一个关键点，OAd的复制不仅取决于其自身的活性，还取决于病毒复制的细胞缺氧环境。在这项研究中，我们构建了一个携带核心蛋白聚糖的 OAd，HRE-Ki67-Decorin，将上游的 Ki67 启动子与缺氧反应元件 (HRE) 序列相结合以驱动腺病毒 E1A。OAd HRE-Ki67-Decorin在缺氧条件下具有更好的复制能力，下调细胞免疫抑制生长因子TGF-β。此外，HRE-Ki67-Decorin 可有效抑制肿瘤生长，并通过在皮下肾癌细胞肿瘤模型中表达 Decorin 参与肿瘤细胞外基质的组装。来自 HRE-Ki67-Decorin 处理的组织的肿瘤切片具有较少的胶原纤维和更多的病毒在肿瘤组织中的传播。这些结果表明，带有核心蛋白聚糖的嵌合 HRE-Ki67 启动子调控的 OAd 可能是一种有效的抗癌治疗策略。