Potent antitumor effect of interleukin-24 gene in the survivin promoter and retinoblastoma double-regulated oncolytic adenovirus.
Potent antitumor effect of interleukin-24 gene in the survivin promoter and retinoblastoma double-regulated oncolytic adenovirus.
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DOI：
10.1089/hum.2008.205
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发表时间：
2009-04
影响因子：
4.2
通讯作者：
Kang-Jian Zhang;Yi Gang Wang;Xin Cao;S. Zhong;R. Wei;Y. Wu;Xue-tian Yue;Gong-chu Li;Xin Yuan Liu
中科院分区：
文献类型：
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作者：
Kang-Jian Zhang;Yi Gang Wang;Xin Cao;S. Zhong;R. Wei;Y. Wu;Xue-tian Yue;Gong-chu Li;Xin Yuan Liu
白细胞介素（IL）-24是一种优良的肿瘤治疗基因。在这项工作中，IL-24被插入到Ad. sp-E1 A（Delta 24）中，Ad. sp-E1 A（Delta 24）是一种溶瘤腺病毒，E1 A基因中有24-bp缺失，其由生存素启动子驱动以形成Ad. sp-E1 A（Delta 24）-IL-24。Ad. sp-E1 A（Delta 24）-IL-24在体外对人鼻咽癌、肝癌、肺癌和宫颈癌细胞系具有优异的抗肿瘤效果，但对正常细胞系L-02和WI 38没有或几乎没有损害。此外，它实现了几乎完全抑制（尽管不是消除）裸鼠中NCI-H460肺癌生长。Ad. sp-E1 A（Delta 24）-IL-24对NCI-H460细胞的抗肿瘤功效明显由凋亡介导，因为其诱导半胱天冬酶-3和聚（ADP-核糖）聚合酶切割。这是首次报道Ad. sp-E1 A（Delta 24）-IL-24在体外具有如此优异、广泛和特异的抗肿瘤作用，并且在体内几乎完全抑制肺肿瘤生长。
Interleukin (IL)-24 is an excellent therapeutic gene for cancer therapy. In this work, IL-24 was inserted into Ad.sp-E1A(Delta24), an oncolytic adenovirus with a 24-bp deletion in the E1A gene, which was driven by the survivin promoter to form Ad.sp-E1A(Delta24)-IL-24. Ad.sp-E1A(Delta24)-IL-24 has an excellent antitumor effect in vitro for human nasopharyngeal, liver, lung, and cervical carcinoma cell lines but does no or little damage to normal cell lines L-02 and WI38. Furthermore, it achieved nearly complete inhibition (although not elimination) of NCI-H460 lung carcinoma growth in nude mice. The antitumor efficacy of Ad.sp-E1A(Delta24)-IL-24 on NCI-H460 cells was clearly mediated by apoptosis, because it induced caspase-3 and poly(ADP-ribose) polymerase cleavage. This is the first report of Ad.sp-E1A(Delta24)-IL-24 with such an excellent, broad, and specific antitumor effect in vitro and nearly complete inhibition of lung tumor growth in vivo.