Title | Arsenic trioxide inhibits viability and induces apoptosis through reactivating the Wnt inhibitor secreted frizzled related protein-1 in prostate cancer cells |
Authors | Zheng, Lei Jiang, Hui Zhang, Zhi-Wei Wang, Ke-Nan Wang, Qi-Fei Li, Quan-Lin Jiang, Tao |
Affiliation | Dalian Med Univ, Affiliated Hosp 1, Dept Urol, 222 Zhong Shan Rd, Dalian 116011, Peoples R China. Fifth Peoples Hosp Dalian, Dept Urol, Dalian, Peoples R China. Beijing Univ, Affiliated Hosp 3, Dept Urol, Beijing 100871, Peoples R China. |
Keywords | arsenic trioxide CpG island methylation demethylation prostate cancer Wnt signaling pathway SFRP1 TUMOR-SUPPRESSOR GENES RADICAL PROSTATECTOMY SIGNALING PATHWAY IN-VITRO EXPRESSION DISEASE GROWTH IDENTIFICATION METHYLATION SFRP1 |
Issue Date | 2016 |
Publisher | ONCOTARGETS AND THERAPY |
Citation | ONCOTARGETS AND THERAPY.2016,9,885-894. |
Abstract | Background: Growing evidence suggests that arsenic trioxide (As2O3) induces apoptosis and inhibits tumor cell growth in prostate cancer (PCa), although details of the mechanism are still inconclusive. We investigated the antitumor effect of As2O3 in human PCa cell lines LNCaP and PC3 and the underlying mechanisms by focusing on the Wnt signaling pathway. Methods: The effect of As2O3 on the viability and apoptosis of PCa cells was investigated by cholecystokinin-8 and flow cytometry. The expression of the related proteins in the Wnt signaling pathway and the downstream target genes of the Wnt signaling pathway was examined by Western blot and quantitative real-time PCR assay. The methylation status of the SFRP1 gene promoter was assessed by bisulfite sequencing. Results: As2O3 inhibited the viability of PCa cells and induced apoptosis of PCa cells in a dose-dependent manner. The protein level of phospho-glycogen synthase kinase-3 beta was upregulated, whereas the protein level of beta-catenin and the mRNA levels of c-MYC, MMP-7, and COX-2 were downregulated in a dose-dependent manner in PCa cells treated with As2O3. In addition, As2O3 upregulated the protein and mRNA levels of secreted frizzled related protein-1, and increased the demethylation of the SFRP1 gene promoter. Conclusion: Our results suggest that As2O3 may inhibit cell viability and induce apoptosis through reactivating the Wnt inhibitor secreted frizzled related protein-1 in both androgen-dependent and -independent human PCa. |
URI | http://hdl.handle.net/20.500.11897/438075 |
ISSN | 1178-6930 |
DOI | 10.2147/OTT.S92129 |
Indexed | SCI(E) PubMed |
Appears in Collections: | 第三医院 |