Abstract

s / Urological Science 26 (2015) 288e293 290 animal study. Age-matchedmale SCIDmice, at 6~8 weeks old, were used in assays for tumor growth and metastasis in an orthotopic graft model. Western blot analysis, reverse-transcriptase polymerase chain reaction (RT-PCR) and Chromatin immunoprecipitation (ChIP) analysis were used for check-up. Results: Osthole suppress the migratory/invasive abilities of prostate cancer cells in wound-closure and transwell invasion assay and metastatic potential in prostate cancer xenograft model. Osthole suppresses the snailinduced EMT in prostate cancer cells and animal model. Mechanistic investigations revealed a signal cascade, namely, osthole inhibiting TGFb/Akt/MAPKs/snail, in which osthole reduced Snail-DNA-binging activity and upregulated E-cadherin expression and subsequently blocked EMT progression. Conclusions: We suggest that osthole inhibits metastasis via transcriptional regulation of E-cad by respectively altering Akt/MAPK/Snail pathways, which was initiated by inhibition of TGF-b productin. These results may warrant clinical trials of osthole in AIPC.

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