Cargando…
AB251. 15-oxospiramilactone inhibits human renal cell carcinoma cell tumorigenesis through inhibition of Wnt/β-catenin signaling
BACKGROUND: Renal-cell carcinoma (RCC) is resistant to almost all chemotherapeutics and radiation therapy. Wnt/β-catenin signaling plays an important role in RCC tumorigenesis, a drug targeting the Wnt signaling is likely to have therapeutic benefit. 15-oxospiramilactone is a new Wnt molecule inhibi...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842552/ http://dx.doi.org/10.21037/tau.2016.s251 |
_version_ | 1782428541128802304 |
---|---|
author | Yi, Xiaoming Shen, Tianyi Zhou, Wenquan Sang, Hong |
author_facet | Yi, Xiaoming Shen, Tianyi Zhou, Wenquan Sang, Hong |
author_sort | Yi, Xiaoming |
collection | PubMed |
description | BACKGROUND: Renal-cell carcinoma (RCC) is resistant to almost all chemotherapeutics and radiation therapy. Wnt/β-catenin signaling plays an important role in RCC tumorigenesis, a drug targeting the Wnt signaling is likely to have therapeutic benefit. 15-oxospiramilactone is a new Wnt molecule inhibiter. In the present study, anti-tumor effects on RCC cells and the involved mechanisms were investigated. METHODS: Human RCC 786-0 and ACHN cells were treated with different concentrations of 15-oxospiramilactone, and cell viability, cell cycle and apoptosis were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein and mRNA expression were assayed by western blotting and quantitative real-time PCR (qPCR). Protein distribution and the association between proteins were assayed by Cytosol and nucleus fractionation and co-immunoprecipitation, respectively. Xenograft assay was used to examine the effect of 15-oxospiramilactone on renal cancer cell proliferation in vivo. RESULTS: 15-oxospiramilactone inhibited the viability of 786-0 and ACHN cells in a dose -dependent manner and it could also significantly suppress the growth of renal carcinoma xenografts and metastasis in nude mice. It also arrested RCC cells at G2/M phase of the cell cycle and induced cell apoptosis. Further study showed that 15-oxospiramilactone inhibited Top-flash reporter activity and decreased the mRNA and/or protein expression of Wnt target genes Axin2, LEF1, NKD1, Cyclin D1 and Survivin, as well as decreased the protein levels of Cdc25c and Cdc2. 15-oxospiramilactone did not affect the cytosol-nuclear distribution, but decreased β-catenin/TCF4 association in RCC cells. CONCLUSIONS: Our data provide first evidence that 15-oxospiramilactone can inhibit cell proliferation in vitro and in vivo, arrest cell cycle at G2/M phase and induce cell apoptosis in RCC cells. The anti-tumor effect is associated with the inhibition of Wnt/β-catenin signaling in RCC cells. The new molecule may be a potential compound for treating renal cell carcinoma. |
format | Online Article Text |
id | pubmed-4842552 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-48425522016-05-09 AB251. 15-oxospiramilactone inhibits human renal cell carcinoma cell tumorigenesis through inhibition of Wnt/β-catenin signaling Yi, Xiaoming Shen, Tianyi Zhou, Wenquan Sang, Hong Transl Androl Urol Printed Abstracts BACKGROUND: Renal-cell carcinoma (RCC) is resistant to almost all chemotherapeutics and radiation therapy. Wnt/β-catenin signaling plays an important role in RCC tumorigenesis, a drug targeting the Wnt signaling is likely to have therapeutic benefit. 15-oxospiramilactone is a new Wnt molecule inhibiter. In the present study, anti-tumor effects on RCC cells and the involved mechanisms were investigated. METHODS: Human RCC 786-0 and ACHN cells were treated with different concentrations of 15-oxospiramilactone, and cell viability, cell cycle and apoptosis were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein and mRNA expression were assayed by western blotting and quantitative real-time PCR (qPCR). Protein distribution and the association between proteins were assayed by Cytosol and nucleus fractionation and co-immunoprecipitation, respectively. Xenograft assay was used to examine the effect of 15-oxospiramilactone on renal cancer cell proliferation in vivo. RESULTS: 15-oxospiramilactone inhibited the viability of 786-0 and ACHN cells in a dose -dependent manner and it could also significantly suppress the growth of renal carcinoma xenografts and metastasis in nude mice. It also arrested RCC cells at G2/M phase of the cell cycle and induced cell apoptosis. Further study showed that 15-oxospiramilactone inhibited Top-flash reporter activity and decreased the mRNA and/or protein expression of Wnt target genes Axin2, LEF1, NKD1, Cyclin D1 and Survivin, as well as decreased the protein levels of Cdc25c and Cdc2. 15-oxospiramilactone did not affect the cytosol-nuclear distribution, but decreased β-catenin/TCF4 association in RCC cells. CONCLUSIONS: Our data provide first evidence that 15-oxospiramilactone can inhibit cell proliferation in vitro and in vivo, arrest cell cycle at G2/M phase and induce cell apoptosis in RCC cells. The anti-tumor effect is associated with the inhibition of Wnt/β-catenin signaling in RCC cells. The new molecule may be a potential compound for treating renal cell carcinoma. AME Publishing Company 2016-04 /pmc/articles/PMC4842552/ http://dx.doi.org/10.21037/tau.2016.s251 Text en 2016 Translational Andrology and Urology. All rights reserved. |
spellingShingle | Printed Abstracts Yi, Xiaoming Shen, Tianyi Zhou, Wenquan Sang, Hong AB251. 15-oxospiramilactone inhibits human renal cell carcinoma cell tumorigenesis through inhibition of Wnt/β-catenin signaling |
title | AB251. 15-oxospiramilactone inhibits human renal cell carcinoma cell tumorigenesis through inhibition of Wnt/β-catenin signaling |
title_full | AB251. 15-oxospiramilactone inhibits human renal cell carcinoma cell tumorigenesis through inhibition of Wnt/β-catenin signaling |
title_fullStr | AB251. 15-oxospiramilactone inhibits human renal cell carcinoma cell tumorigenesis through inhibition of Wnt/β-catenin signaling |
title_full_unstemmed | AB251. 15-oxospiramilactone inhibits human renal cell carcinoma cell tumorigenesis through inhibition of Wnt/β-catenin signaling |
title_short | AB251. 15-oxospiramilactone inhibits human renal cell carcinoma cell tumorigenesis through inhibition of Wnt/β-catenin signaling |
title_sort | ab251. 15-oxospiramilactone inhibits human renal cell carcinoma cell tumorigenesis through inhibition of wnt/β-catenin signaling |
topic | Printed Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842552/ http://dx.doi.org/10.21037/tau.2016.s251 |
work_keys_str_mv | AT yixiaoming ab25115oxospiramilactoneinhibitshumanrenalcellcarcinomacelltumorigenesisthroughinhibitionofwntbcateninsignaling AT shentianyi ab25115oxospiramilactoneinhibitshumanrenalcellcarcinomacelltumorigenesisthroughinhibitionofwntbcateninsignaling AT zhouwenquan ab25115oxospiramilactoneinhibitshumanrenalcellcarcinomacelltumorigenesisthroughinhibitionofwntbcateninsignaling AT sanghong ab25115oxospiramilactoneinhibitshumanrenalcellcarcinomacelltumorigenesisthroughinhibitionofwntbcateninsignaling |