School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
Amino Acids. 2018 Aug;50(8):1121-1129. doi: 10.1007/s00726-018-2589-4. Epub 2018 May 23.
The present research has been carried out to elicit the mechanism of antiangiogenic activity of a fusion peptide P2. Peptide P2 was designed by the connection of a heptapeptide MMP inhibitor to ES-2, a fragment of Endostatin. In a previous study, P2 demonstrated strong antiangiogenic and antitumor effect, and the current work explains the antiangiogenic mechanism of P2 through endothelial cell proliferation and apoptosis. In our study, it was shown that P2 inhibited HUVECs proliferation at a low serum concentration and this effect might be achieved through arresting cell cycle by decreasing the expression level of Cyclin D1. In addition, P2 was found to induce apoptosis of HUVECs. Using Western blot, it was indicated that P2 induced the cleavage of Caspase-3, the hallmark protease of apoptosis. The activation and expression of the upstream regulator Caspase-9 can also be affected by P2 treatment. Furthermore, P2 reduced the protein level of antiangiogenic factors Bcl-xL and Bcl-2. These results revealed that P2 regulates endothelial cell apoptosis through intrinsic apoptotic pathway.
本研究旨在探讨融合肽 P2 的抗血管生成活性的作用机制。肽 P2 是通过将七肽 MMP 抑制剂与 ES-2（Endostatin 的一个片段）连接而设计的。在之前的研究中，P2 表现出强烈的抗血管生成和抗肿瘤作用，目前的工作通过内皮细胞增殖和凋亡来解释 P2 的抗血管生成机制。在我们的研究中，表明 P2 在低血清浓度下抑制 HUVECs 的增殖，这一作用可能通过降低 Cyclin D1 的表达水平来阻止细胞周期。此外，发现 P2 诱导 HUVECs 凋亡。Western blot 表明，P2 诱导了凋亡标志性蛋白酶 Caspase-3 的切割。P2 处理还可以影响上游调节因子 Caspase-9 的激活和表达。此外，P2 降低了抗血管生成因子 Bcl-xL 和 Bcl-2 的蛋白水平。这些结果表明，P2 通过内在凋亡途径调节内皮细胞凋亡。
