(PD1-6) By inhibiting snail signaling, osthole suppresses the emt-mediated metastatic ability in prostate cancer
  • 2015-11-30,
  • 上傳者: TUA秘書處,
  •  0
1台北市立萬芳醫院 泌尿科、2教研部;
3臺北醫學大學 臨床醫學研究所
By inhibiting snail signaling, osthole suppresses the emt-mediated metastatic ability in prostate cancer
Yu-Ching Wen1,3, Liang-Ming Lee1*, Ming-Hsien Chien2,3*
1Department of Urology、2Department of Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Graduate Institute of Clinical Medicine, collage of medicine, Taipei Medical University, Taipei, Taiwan
To evaluate the anti-metastatic potential of osthole in prostate cancer cells and xenograft animal model.
Materials and Methods:
The PC3 and DU145 human adrogen independent prostate cancer (AIPC) cell lines were obtained from American Type Culture Collection for cell assay. PC-3M, a highly metastatic subline derived from the hepatic metastasis of PC-3 in nude mice, was used for xenograft animal study. Age-matched male SCID mice, 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.
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 snail-induced EMT in prostate cancer cells and animal model. Mechanistic investigations revealed a signal cascade, namely, osthole inhibiting TGF-βàAktàMAPKsàsnail, in which osthole reduced Snail-DNA-binging activity and upregulated E-cadherin expression and subsequently blocked EMT progression.
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-β productin. These results may warrant clinical trials of osthole in AIPC.
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    2015-11-30 10:33:00
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