Xie Junye, Li Fu, Cai Yuling, Zhang Jinting, Zhang Yibo, Zhai Zhaodong, Su Zijian, Chen Xue, Lei Minghua, Liu Rongzhan, Li Weicai, Kang Dianlong, Chen Xiaojia, Hong An
Institute of Biomedicine & Department of Cell Biology, College of Life Science and Technology, Guangdong Province Key Laboratory of Bioengineering Medicine, Guangdong Provincial Biotechnology Drug & Engineering Technology Research Center; National Engineering Research Center of Genetic Medicine, Ji'nan University, Guangzhou, 510632, China.
The First Affiliated Hospital, Ji'nan University, Guangzhou, 510630, China.
Heliyon. 2023 Jul 14;9(7):e18240. doi: 10.1016/j.heliyon.2023.e18240. eCollection 2023 Jul.
Shark cartilage was created as a cancer-fighting diet because it was believed to have an element that may suppress tumor growth. Due to overfishing, sharks have become endangered recently, making it impossible to harvest natural components from shark cartilage for therapeutic development research. Previously, we identified a peptide SAIF from shark cartilage with an-tiangiogenic and anti-tumor effects, successfully expressed it in by using genetic engineering techniques. However, we did not elucidate the specific target of SAIF and its antiangiogenic molecular mechanism, which hindered its further drug development. Therefore, in this work, the exact mechanism of action was studied using various techniques, including cellular and in vivo animal models, computer-aided simulation, molecular target capture, and transcriptome sequencing analysis. With VEGF-VEGFR2 interaction and preventing the activation of VEGFR2/ERK signaling pathways, SAIF was discovered to decrease angiogenesis and hence significantly limit tumor development. The findings further demonstrated SAIF's strong safety and pharmaceutically potential. The evidence showed that SAIF, which is expressed by, is a potent and safe angiogenesis inhibitor and might be developed as a candidate peptide drug for the treatment of solid tumors such as hepatocellular carcinoma and other conditions linked with angiogenic overgrowth.
鲨鱼软骨曾被开发为一种抗癌饮食,因为人们认为它含有一种可能抑制肿瘤生长的成分。由于过度捕捞,鲨鱼最近已濒临灭绝,这使得从鲨鱼软骨中获取天然成分用于治疗性开发研究变得不可能。此前,我们从鲨鱼软骨中鉴定出一种具有抗血管生成和抗肿瘤作用的肽SAIF,并利用基因工程技术在[具体表达系统未提及]中成功表达了它。然而,我们并未阐明SAIF的具体靶点及其抗血管生成分子机制,这阻碍了其进一步的药物开发。因此,在这项工作中,我们使用了多种技术,包括细胞和体内动物模型、计算机辅助模拟、分子靶点捕获和转录组测序分析,来研究其确切的作用机制。通过VEGF-VEGFR2相互作用并阻止VEGFR2/ERK信号通路的激活,发现SAIF可减少血管生成,从而显著限制肿瘤发展。这些发现进一步证明了SAIF具有很强的安全性和药学潜力。证据表明,由[具体表达系统未提及]表达的SAIF是一种有效且安全的血管生成抑制剂,可能被开发为一种候选肽药物,用于治疗实体瘤,如肝细胞癌以及其他与血管生成过度相关的病症。