鲨鱼软骨被研发为一种抗癌饮食，因为人们认为它含有一种可能能抑制肿瘤生长的成分。由于过度捕捞，鲨鱼近年来已成为濒危物种，因此无法从鲨鱼软骨中采集天然成分进行治疗开发研究。之前，我们从鲨鱼软骨中鉴定出具有抗血管生成和抗肿瘤效果的肽SAIF，并成功利用基因工程技术在大肠杆菌中进行表达。然而，我们尚未阐明SAIF的具体靶点和其抗血管生成的分子机制，这妨碍了进一步的药物开发。因此，在本研究中，我们利用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等多种技术，对其作用机制进行了详细研究。结果发现，SAIF通过与VEGF-VEGFR2相互作用并阻断VEGFR2/ERK信号通路的激活，降低了血管生成，从而显著限制了肿瘤的发展。这些发现进一步证明了SAIF的安全性和药学潜力。实验证据表明，由...表达的SAIF是一种强有效且安全的血管生成抑制剂，可能成为肝细胞癌等固体肿瘤治疗的候选肽类药物。© 2023 作者

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 Escherichia coli 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.© 2023 The Authors.