کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2116255 | 1084806 | 2013 | 11 صفحه PDF | دانلود رایگان |
• An FGF8b gN helix derived peptide (8b-13) inhibits proliferation of prostate cancer cells.
• 8b-13 arrests the cell cycle at the G0/G1 phase, and down-regulated the expression of cyclinD1.
• 8b-13 reduces the activation of Erk1/2, P38, and Akt cascades
• 8b-13 alters the expression of certain proteins involved in the regulation of proliferation.
• Our findings suggest that 8b-13 may exert an antitumor effect in cancers with high FGF8b levels.
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.
Journal: Cancer Letters - Volume 339, Issue 2, 10 October 2013, Pages 226–236