Antitumor potential of a synthetic interferon-alpha/PLGF-2 positive charge peptide hybrid molecule in pancreatic cancer cells

作者：Yin Hongmei; Chen Naifei; Guo Rui; Wang Hong; Li Wei; Wang Guanjun; Cui Jiuwei^*; Jin Haofan; Hu Ji Fan

来源：Scientific Reports, 2015, 5(1): 16975.

DOI：10.1038/srep16975

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 (IFN alpha) 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 IFN alpha. For this, we constructed a synthetic interferon hybrid molecule (SIF alpha) by fusing the positively charged PLGF-2 peptide to the C-terminus of the human IFN alpha. Using human pancreatic cell lines (ASPC and CFPAC1) as a model system, we found that SIF alpha exhibited a significantly higher activity than did the wild-type IFN alpha in inhibiting the tumor cell growth. The enhanced activity of the synthetic SIF alpha 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 SIF alpha as a novel antitumor agent.

• 出版日期2015-11-20
• 单位吉林大学