The antitumor activity of TRAIL and IL-24 with replicating oncolytic adenovirus in colorectal cancer
The antitumor activity of TRAIL and IL-24 with replicating oncolytic adenovirus in colorectal cancer
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DOI：
10.1038/sj.cgt.7700969
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发表时间：
2006-11-01
影响因子：
6.4
通讯作者：
Liu, X.
中科院分区：
文献类型：
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作者：
Zhao, L.;Dong, A.;Liu, X.
将恶性黑色素瘤分化相关基因7（Mda-7）/ IL-24克隆入腺病毒ZD 55（E1 B55缺失的腺病毒）中，构建成ZD 55-IL-24，其抗肿瘤效果明显优于Ad-IL-24。由于其良好的抗肿瘤特性，ZD 55-IL-24已被用于临床前研究。但是单独使用ZD 55-IL-24仍然不能完全根除所有裸鼠中已建立的肿瘤。研究表明，IL-24可诱导和增强肿瘤坏死因子超家族成员肿瘤坏死因子相关凋亡诱导配体（TRAIL）的活性。因此，在本研究中进行了ZD 55-IL-24和ZD 55-TRAIL的组合使用。与单独使用ZD 55-IL-24或ZD 55-TRAIL相比，联合使用ZD 55-IL-24和ZD 55-TRAIL可以在体外诱导更显著的癌细胞凋亡。两种复制型腺病毒的组合比单一溶瘤腺病毒具有更好的体内抗肿瘤活性，并导致所有治疗小鼠中异种移植肿瘤的完全根除。在用ZD 55-IL-24感染的肿瘤细胞中观察到TRAIL的上调，并且凋亡级联调节剂的研究表明ZD 55-IL-24可以通过死亡受体的TNF家族进一步增强凋亡的激活。我们首次证明了ZD 55-IL-24与ZD 55-TRAIL联合用于癌症靶向治疗的潜在治疗效果。
Melanoma differentiation associated gene-7 (Mda-7)/ IL-24 was previously cloned into ZD55 (an adenovirus with E1B55 deleted) to form ZD55-IL-24, which had much better antitumor effect than Ad-IL-24. According to its good antitumor properties, ZD55-IL-24 has been used in preclinical studies. But ZD55-IL-24 alone still could not completely eradicate established tumors in all nude mice. It was reported that IL-24 could induce and enhance the activity of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (a member of tumor necrosis factor (TNF) superfamily). Accordingly, the combined use of ZD55-IL-24 and ZD55-TRAIL was carried out in this study. Treatment with both ZD55-IL-24 and ZD55-TRAIL could induce more significant apoptosis in cancer cells in vitro compared with ZD55-IL-24 or ZD55-TRAIL alone. The combination of the two replicative adenoviruses had better antitumor activity in vivo than that of single oncolytic adenovirus and led to complete eradication of xenograft tumors in all treated mice. Upregulation of TRAIL was observed in tumor cells infected with ZD55-IL-24 and studies of the apoptotic cascade regulators indicate that ZD55-IL-24 could further enhance the activation of apoptosis through the TNF family of death receptors. We demonstrated for the first time the potential therapeutic effect of combined ZD55-IL-24 with ZD55-TRAIL for the targeted therapy of cancer.