Zhang Kang Jian, Wang Yi Gang, Cao Xin, Zhong Su Yang, Wei Rui Cheng, Wu Yu Mei, Yue Xue Tian, Li Gong Chu, Liu Xin Yuan
School of Life Sciences, Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Hum Gene Ther. 2009 Aug;20(8):818-30. doi: 10.1089/hum.2008.205.
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.
白细胞介素（IL）-24是一种用于癌症治疗的优秀治疗基因。在本研究中，将IL-24插入Ad.sp-E1A(Delta24)，这是一种在E1A基因中有24个碱基对缺失的溶瘤腺病毒，由生存素启动子驱动，形成Ad.sp-E1A(Delta24)-IL-24。Ad.sp-E1A(Delta24)-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作用，但对正常细胞系L-02和WI38没有或几乎没有损伤。此外，它在裸鼠中几乎完全抑制（尽管未消除）NCI-H460肺癌的生长。Ad.sp-E1A(Delta24)-IL-24对NCI-H460细胞的抗肿瘤功效显然是通过凋亡介导的，因为它诱导了caspase-3和聚（ADP-核糖）聚合酶的裂解。这是关于Ad.sp-E1A(Delta24)-IL-24在体外具有如此优异、广泛且特异性的抗肿瘤作用以及在体内几乎完全抑制肺肿瘤生长的首次报道。
