A peptide derivative serves as a fibroblast growth factor 2 antagonist in human gastric cancer

作者:Fan, Lei; Li, Wulan; Ying, Shilong; Shi, Lingyi; Wang, Zhe; Chen, Gaozhi; Ye, Hui; Wu, Xiaoping*; Wu, Jianzhang; Liang, Guang; Li, Xiaokun
来源:Tumor Biology, 2015, 36(9): 7233-7241.
DOI:10.1007/s13277-015-3435-x

摘要

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.