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携带人白细胞介素-24的腺病毒在体外抑制神经母细胞瘤细胞增殖,并在体内抑制异种移植肿瘤生长。

Adenovirus arming human IL-24 inhibits neuroblastoma cell proliferation in vitro and xenograft tumor growth in vivo.

作者信息

Zhuo Baobiao, Wang Rong, Yin Yiyu, Zhang Hongwei, Ma Tongsheng, Liu Fengli, Cao Hui, Shi Yingchun

机构信息

Department of Surgery, Xuzhou Children's Hospital, 18 Suti North Road, Xuzhou, Jiangsu, 221006, China.

出版信息

Tumour Biol. 2013 Aug;34(4):2419-26. doi: 10.1007/s13277-013-0792-1. Epub 2013 Apr 23.

Abstract

Data have increasingly shown that interlukin-24 (IL-24) has growth suppression activity and can induce apoptosis in a broad spectrum of tumor cells. However, the therapeutic effect of IL-24 on human neuroblastoma has rarely been explored. In this study, we used a human neuroblastoma cell line (SH-SY5Y) to reveal the effect of adenovirus-mediated IL-24 (Ad-IL24) gene therapy for neuroblastoma. We showed that Ad-IL24 effectively inhibited the proliferation of SH-SY5Y cells in vitro by conspicuously inducing apoptosis. To further explore the molecular mechanism by which Ad-IL24 induced apoptosis in SH-SY5Y tumor cells, we found that Ad-IL24 increased the expression of Bax and promoted the activation of caspase-3, while decreasing Bcl-2 levels. We also demonstrated that Ad-IL24 significantly inhibited tumor growth in vivo in a xenograft neuroblastoma tumor in athymic nude mice. In summary, Ad-IL24 overexpression exerted potent antitumor activity via inducing apoptosis in neuroblastoma cells. Therefore, IL-24 has the potential to serve as an agent for gene therapy in the treatment of neuroblastoma.

摘要

越来越多的数据表明,白细胞介素-24(IL-24)具有生长抑制活性,可诱导多种肿瘤细胞凋亡。然而,IL-24对人类神经母细胞瘤的治疗效果鲜有研究。在本研究中,我们使用人类神经母细胞瘤细胞系(SH-SY5Y)来揭示腺病毒介导的IL-24(Ad-IL24)基因治疗对神经母细胞瘤的作用。我们发现Ad-IL24通过显著诱导凋亡有效地抑制了SH-SY5Y细胞在体外的增殖。为进一步探究Ad-IL24诱导SH-SY5Y肿瘤细胞凋亡的分子机制,我们发现Ad-IL24增加了Bax的表达并促进了caspase-3的激活,同时降低了Bcl-2水平。我们还证明,Ad-IL24在无胸腺裸鼠的异种移植神经母细胞瘤肿瘤中显著抑制了体内肿瘤生长。总之,Ad-IL24过表达通过诱导神经母细胞瘤细胞凋亡发挥了强大的抗肿瘤活性。因此,IL-24有潜力作为一种基因治疗药物用于神经母细胞瘤的治疗。

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