| AIM: Fibroblast growth factor8b (FGF8b) was up-regulated in a large proportion ofprostate cancer, and plays a critical role in prostate carcinogenesis and cancerprogression.8b-13, a gN helix domain derived short peptide based on theFGF8b-FGFR structure analysis in first time. We investigated the mechanism and theeffects of8b-13on the prostate cancer cell growth.Methods: DU-145and PC-3cells were used as target cells for investigation. Cellviability was measured by MTT. Cell cycle progression was determined by propidiumiodide staining and flow cytometry. The activation of Erk1/2, P38, Akt and theexpression of proliferation-associated protein (PCNA and cyclinD1) were measuredwith western blots. Two-dimensional electrophoresis and mass spectrometrytechnology were applied to analyze the mechanisms of8b-13for specificdifferentially expressed proteins, and the result of the proteomics was verified bywestern blotting and Q-PCR.Results: In this study, the synthetic peptides inhibited proliferation of prostate cancercell lines including DU-145and PC-3cells by specific disturbing the interactionbetween FGF8b and its receptors. Further investigation indicated that8b-13arrestedthe cell cycle at the G0/G1phase, reduced the activation of Erk1/2, P38, and Aktcascades, and down-regulation of G1/S-specific cyclinD1expression. In addition,Eight differentially expressed proteins influenced by8b-13were identified, such asPAFAH1B2、ESD and CRABP2et al. The expression levels of four proteins weredecreased by FGF8b stimulation alone and increased by addition of8b-13, whileother four proteins were down-regulated by8b-13. Suppress the expression ofCRABP2and PCNA, and up-regulation of PAFAH1B2and ESD expression maypartly contribute to the inhibitory effect of8b-13peptides on the cellular proliferation.Conclutions: These data not only suggest8b-13has a potential antitumor effect onprostate cancer, but also confirm the essential role of the gN helix domain inmediating the activities of FGF8b. |
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