title: A peptide derivative serves as a fibroblast growth factor 2 antagonist in human gastric cancer.
abstract: Fibroblast growth factor 2 (FGF2) plays a critical role in tumorigenesis and progression of solid tumor and is upregulated in gastric carcinoma serum. Therefore, it is regarded as a potential therapeutic target of human gastric cancer. Suppression of bioactivities of FGF2 may contribute to human gastric cancer therapy. Herein, we obtained a novel FGF2-binding peptide derivative (named P32), which originated from a previously isolated P7 peptide with poor stability. We proved that P32, which had a half-life in human plasma up to 12 h, enhanced stability and exerted strong inhibitory effect on FGF2-induced cell proliferation and invasion in human gastric cancer cell lines. Further investigations revealed that the underlying anti-proliferation mechanisms of P32 in vitro included arresting FGF2-stimulated cells at the G0/G1 phase and reducing the activation of AKT and Erk1/2 cascades. The FGF2-binding peptide derivative P32 has improved stability, is relatively safe, and may have therapeutic potential in FGF2-driven gastric cancer.
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.|Department of Pharmacy, Jinhua Municipal Central Hospital, Jinhua, 321000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.|College of Information Science and Computer Engineering, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Wulan
authors.initials: W
authors.lastname: Li
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Ying
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Shi
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Gaozhi
authors.initials: G
authors.lastname: Chen
authors.affiliation: School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ye
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China. wjzwzmu@163.com.|Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, 510632, China. wjzwzmu@163.com.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wu
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China. wxpjnu@163.com.
authors.forename: Jianzhang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
mesh_terms: D063646:Carcinogenesis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000235:genetics; D007700:Kinetics; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009361:Neoplasm Invasiveness / Q000235:genetics; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D020349:Surface Plasmon Resonance
chemical_list: D055767:Immobilized Proteins; D010455:Peptides; D016222:Fibroblast Growth Factor 2
keywords: Anti-proliferation; FGF2 binding; Half-life; Non-toxicity; Peptide derivative