Bovine Hemoglobin Derived Peptide Asn-Phe-Gly-Lys Inhibits Pancreatic Cancer Cells Metastasis by Targeting Secreted Hsp90α.

Pancreatic cancer is a digestive system malignant carcinoma with poor prognosis. The majority of patients are diagnosed with metastatic disease, which is also the leading cause of pancreatic cancer death. The aim of this study was to investigate the antimetastatic effect of Asn-Phe-Gly-Lys (NFGK), a tetrapeptide derived from bovine hemoglobin pepsin hydrolysate, on human pancreatic cancer cell line MIAPaCa-2. Wound healing assay and transwell invasion assay results showed that NFGK inhibited MIAPaCa-2 cell migration and invasion dose-dependently. Cell proliferation assay data showed that NFGK had slight cytotoxicity on MIAPaCa-2 cells. Fluorescence confocal imaging data revealed that NFGK targeted the cell membrane of MIAPaCa-2. Molecular docking data displayed that NFGK bond to the N-terminus ATP-binding pocket of secreted heat shock protein 90α (Hsp90α). Western blotting results further proved that NFGK inhibited secreted Hsp90α and downstream matrix metalloproteinase-9 (MMP-9) level dose dependently, while it did not inhibit intracellular Hsp90 and cyclin-dependent-kinase 4 (CDK4). All above results demonstrated that bovine hemoglobin derived peptide NFGK inhibited pancreatic cancer cell metastasis by targeting secreted Hsp90α and its downstream MMP-9.

PRACTICAL APPLICATION: Peptide NFGK comes from bovine hemoglobin, which is digested by pepsin in stomach after eating. After digesting to NFGK, bovine hemoglobin will obtain new function of inhibiting pancreatic cancer cell metastasis without dramatic cell toxicity. These means NFGK may help those patients who are suffering pancreatic cancer to avoid cancer cell metastasis without too much side effect.