A short peptide derived from the gN helix domain of FGF8b suppresses the growth of human prostate cancer cells

作者:Li, Tao; Luo, Wu; He, Dan; Wang, Ruixue; Huang, Yadong; Zeng, Xiangfeng; Wang, Wenhui; Chen, Xilei; Gao, Susu; Yu, Yonglin; Li, Xiaokun; Wu, Xiaoping*
来源:Cancer Letters, 2013, 339(2): 226-236.
DOI:10.1016/j.canlet.2013.06.001

摘要

Previous studies have demonstrated that fibroblast growth factor 8b (FGF8b) is up-regulated in a large proportion of prostate cancer patients and that it plays a key role in prostate carcinogenesis. In this study, we designed and synthesized a gN helix domain derived short peptide (termed 8b-13) based on the analysis of the FGF8b-FGFR structure. The synthetic peptides inhibited the proliferation of prostate cancer cell lines, including PC-3 and DU-145 cells. Further investigations indicated that 8b-13 arrested the cell cycle at the G0/G1 phase, reduced the activation of the Erk1/2, P38, and Akt cascades, and down-regulated the expression of G1/S-specific cyclinD1. The suppression of DNA synthesis and the G1 to S phase transition due to the expression of proteins related to proliferation and cell cycle progression may contribute to the inhibitory effect of 8b-13 peptides on cellular proliferation. Our results not only suggest that 8b-13 exerts an antitumor effect in prostate cancer but also confirm the essential role of the gN helix domain in mediating the activity of FGF8b.