Author/Authors :
Li، نويسنده , , Tao and Luo، نويسنده , , Wu and He، نويسنده , , Dan and Wang، نويسنده , , Ruixue and Huang، نويسنده , , Yadong and Zeng، نويسنده , , Xiangfeng and Wang، نويسنده , , Wenhui and Chen، نويسنده , , Xilei and Gao، نويسنده , , Susu and Yu، نويسنده , , Yonglin and Li، نويسنده , , Xiaokun and Wu، نويسنده , , Xiaoping، نويسنده ,
Abstract :
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.
Keywords :
FGF8b , Proliferation , prostate cancer , gN helix