Wei Xubin, Liu Li, Wang Gang, Li Wei, Xu Ke, Qi Hongyan, Liu Hong, Shen Jing, Li Zhongjie, Shao Jimin
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, P.R. China.
Oncol Rep. 2015 Jan;33(1):111-8. doi: 10.3892/or.2014.3563. Epub 2014 Oct 22.
The Ad5/11 chimeric oncolytic adenovirus represents a promising new platform for anticancer therapy. Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hematopoietic progenitor cells and is the most common malignant myeloid disorder in adults. Myeloid and other hematopoietic cell lineages are involved in the process of clonal proliferation and differentiation. In the present study, we aimed to ascertain whether chimeric oncolytic adenovirus-mediated transfer of the human interleukin-24 (IL-24) gene induces enhanced antitumor potency. Our results showed that the Ad5/11 chimeric oncolytic adenovirus carrying hIL-24 (AdCN205‑11-IL-24) produced high levels of hIL-24 in AML cancer cells, as compared with the Ad5 oncolytic adenovirus expressing hIL-24 (AdCN205-IL-24). AdCN205-11-IL-24 specifically induced a cytotoxic effect on AML cancer cells, but had little or no effect on a normal cell line. AdCN205-11-IL-24 induced higher antitumor activity in AML cancer cells by inducing apoptosis in vitro. This study suggests that transfer of IL-24 by an Ad5/11 chimeric oncolytic adenovirus may be a potent antitumor approach for AML cancer therapy.
Ad5/11嵌合溶瘤腺病毒是一种很有前景的抗癌治疗新平台。急性髓系白血病（AML）是造血祖细胞的一种异质性克隆性疾病，是成人中最常见的恶性髓系疾病。髓系和其他造血细胞谱系参与克隆增殖和分化过程。在本研究中，我们旨在确定嵌合溶瘤腺病毒介导的人白细胞介素-24（IL-24）基因转移是否能增强抗肿瘤效力。我们的结果表明，与表达hIL-24的Ad5溶瘤腺病毒（AdCN205-IL-24）相比，携带hIL-24的Ad5/11嵌合溶瘤腺病毒（AdCN205‑11-IL-24）在AML癌细胞中产生高水平的hIL-24。AdCN205-11-IL-24对AML癌细胞具有特异性细胞毒性作用，但对正常细胞系几乎没有影响或没有影响。AdCN205-11-IL-24通过在体外诱导凋亡，在AML癌细胞中诱导更高的抗肿瘤活性。本研究表明，Ad5/11嵌合溶瘤腺病毒介导的IL-24转移可能是一种有效的AML癌症治疗抗肿瘤方法。
