A Novel Peptide from Abalone ( Haliotis discus hannai ) to Suppress Metastasis and Vasculogenic Mimicry of Tumor Cells and Enhance Anti-Tumor Effect In Vitro

• Published in: Marine drugs 2019-04, Vol.17 (4), p.244
• Main Authors: Gong, Fang, Chen, Mei-Fang, Zhang, Yuan-Yuan, Li, Cheng-Yong, Zhou, Chun-Xia, Hong, Peng-Zhi, Sun, Sheng-Li, Qian, Zhong-Ji
• Format: Article
• Language: English
• Subjects: abalone; Adult; AKT protein; Angiogenesis; Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - pharmacology; Animals; Anticancer properties; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cancer therapies; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cytotoxicity; eIF-2 Kinase - metabolism; Fibrosarcoma; Gastropoda - chemistry; Haliotis discus hannai; HIF-1α; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen bonds; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factor 1a; Lead compounds; Male; MAP Kinase Signaling System - drug effects; Marine molluscs; Matrix Metalloproteinases - metabolism; Metabolites; Metastases; Metastasis; Mimicry; MMPs; Mode of action; Molecular docking; Mutation; Neoplasm Metastasis; Neoplasms; Neoplasms - blood supply; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; NF-kappa B - metabolism; NF-κB protein; Nutrition; Oncogene Protein v-akt - metabolism; peptide; Peptides; Peptides - chemistry; Peptides - isolation & purification; Peptides - pharmacology; Phosphorylation; Proteins; Ribosomal Protein S6 Kinases, 70-kDa - metabolism; Spheroids, Cellular - drug effects; TOR protein; TOR Serine-Threonine Kinases - metabolism; Tumor cells; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; vasculogenic mimicry
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md17040244

Vasculogenic mimicry (VM) formed by tumor cells plays a vital role in the progress of tumor, because it provides nutrition for tumor cells and takes away the metabolites. Therefore, the inhibition of VM is crucial to the clinical treatment of tumors. In this study, we investigated the anti-tumor effect of a novel peptide, KVEPQDPSEW (AATP), isolated from abalone ( ) on HT1080 cells by migration, invasion analysis and the mode of action. The results showed that AATP effectively inhibited MMPs by blocking MAPKs and NF-κB pathways, leading to the downregulation of metastasis of tumor cells. Moreover, AATP significantly inhibited VM and pro-angiogenic factors, including VEGF and MMPs by suppression of AKT/mTOR signaling. In addition, molecular docking was used to study the interaction of AATP and HIF-1α, and the results showed that AATP was combined with an active site of HIF-1α by a hydrogen bond. The effect of AATP on anti-metastatic and anti-vascular in HT1080 cells revealed that AATP may be a potential lead compound for treatment of tumors in the future.