Antitumor potential of a synthetic interferon-alpha/PLGF-2 positive charge peptide hybrid molecule in pancreatic cancer cells.
Antitumor potential of a synthetic interferon-alpha/PLGF-2 positive charge peptide hybrid molecule in pancreatic cancer cells.
复制标题
合成干扰素-α/PLGF-2 正电荷肽杂合分子在胰腺癌细胞中的抗肿瘤潜力
DOI：
10.1038/srep16975
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发表时间：
2015-11-20
影响因子：
4.6
通讯作者：
Hu JF
中科院分区：
文献类型：
--
作者：
Yin H;Chen N;Guo R;Wang H;Li W;Wang G;Cui J;Jin H;Hu JF
胰腺癌是最具侵袭性的恶性疾病，是美国男性和女性癌症相关死亡的第四大原因。干扰素α (IFNα)已被用于治疗胰腺癌，但其抗肿瘤活性较低，严重阻碍了其临床应用。我们使用“cDNA - in-frame fragment library”筛选方法来鉴定能够增强干扰素抗肿瘤活性的短肽。从胎盘生长因子-2 （PLGF-2）的c端提取的一种带正电荷的短肽可以增强IFNα的活性。为此，我们将带正电的PLGF-2肽融合到人干扰素α的c端，构建了一个人工合成的干扰素杂交分子（SIFα）。以人胰腺细胞系（ASPC和CFPAC1）为模型系统，我们发现SIFα在抑制肿瘤细胞生长方面表现出明显高于野生型IFNα的活性。合成的SIFα活性增强与干扰素通路靶基因激活和细胞膜受体结合增加有关。本研究证明了一种合成的SIFα作为一种新型抗肿瘤药物的潜力。
Pancreatic cancer is the most aggressive malignant disease, ranking as the fourth leading cause of cancer-related death among men and women in the United States. Interferon alpha (IFNα) has been used to treat pancreatic cancer, but its clinical application has been significantly hindered due to the low antitumor activity. We used a “cDNA in-frame fragment library” screening approach to identify short peptides that potentiate the antitumor activity of interferons. A short positively charged peptide derived from the C-terminus of placental growth factor-2 (PLGF-2) was selected to enhance the activity of IFNα. For this, we constructed a synthetic interferon hybrid molecule (SIFα) by fusing the positively charged PLGF-2 peptide to the C-terminus of the human IFNα. Using human pancreatic cell lines (ASPC and CFPAC1) as a model system, we found that SIFα exhibited a significantly higher activity than did the wild-type IFNα in inhibiting the tumor cell growth. The enhanced activity of the synthetic SIFα was associated with the activation of interferon pathway target genes and the increased binding of cell membrane receptor. This study demonstrates the potential of a synthetic SIFα as a novel antitumor agent.