Novaferon, a novel recombinant protein produced by DNA-shuffling of IFN-α, shows antitumor effect in vitro and in vivo
Novaferon, a novel recombinant protein produced by DNA-shuffling of IFN-α, shows antitumor effect in vitro and in vivo
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DOI：
10.1186/1475-2867-14-8
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发表时间：
2014-01-27
影响因子：
5.8
通讯作者：
Wang, Junzhi
中科院分区：
文献类型：
--
作者：
Li, Meng;Rao, Chunming;Wang, Junzhi
目的：重组抗肿瘤/抗病毒蛋白（Novaferon，Nova）是一种新型干扰素，采用DNA改组和高通量筛选（HTS）相结合的人工设计技术，制备而成。方法：对Nova和重组人干扰素α-2b（rhIFN-α 2b）进行体外抗肿瘤、抗病毒等生物学活性研究，并进行裸鼠体内抗肿瘤活性研究。采用流式细胞术、HE染色、免疫组化等组织病理学分析及表面等离子体共振分析等方法对Nova的抗肿瘤作用机制进行研究。Nova的抗肿瘤机制可能与S期阻滞、促凋亡和抑制肿瘤血管生成有关。Nova与IFN受体2（IFNR 2）的结合亲和力高于rhIFN-α 2b，这可能是其抗肿瘤作用强于rhIFN-α 2b的原因之一。结论：Nova具有较强的抗肿瘤活性，有望成为一种潜在的有效的肿瘤治疗药物。
Objective: A recombinant antitumor/antiviral protein (Novaferon, Nova) is a new type of interferon, which is produced by artificial design technology combining DNA-shuffling and High Throughput Screening (HTS).Methods: The in vitro biological activities, such as anti-tumor activity and antiviral activity of Nova and recombinant human interferon alpha-2b (rhIFN-alpha 2b) was performed; in vivo anti-tumor activity in nude mice was also tested. Flow cytometry, histo-pathological analysis including HE staining and immunohistochemistry, and surface plasmon resonance assay were performed to investigate the underlying mechanisms analysis.Results: Nova exhibited stronger anti-cancer effects compared to rhIFN-alpha 2b in vitro and in vivo. The antitumor mechanisms of Nova may be related to S phase arrest, pro-apoptosis, and inhibition of tumor angiogenesis. Moreover, Nova exhibited a higher binding affinity for IFN receptor 2 (IFNR2) than rhIFN-alpha 2b, which is one of the possible reasons accounting for its stronger actions against tumor cells compared with rhIFN-alpha 2b.Conclusion: Nova has strong antitumor activity and could be a potentially effective therapeutic drug for cancer.