AB251. 15-oxospiramilactone inhibits human renal cell carcinoma cell tumorigenesis through inhibition of Wnt/β-catenin signaling
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AB251. 15-oxospiramilactone inhibits human renal cell carcinoma cell tumorigenesis through inhibition of Wnt/β-catenin signaling

Xiaoming Yi, Tianyi Shen, Wenquan Zhou, Hong Sang

Nanjing General Hospital of Nanjing Military Region, Nanjing 210002, China


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.

Keywords: 15-oxospiramilactone; renal cell carcinoma (RCC) cell; Wnt/β-catenin signaling


doi: 10.21037/tau.2016.s251


Cite this abstract as: Yi X, Shen T, Zhou W, Sang H. 15-oxospiramilactone inhibits human renal cell carcinoma cell tumorigenesis through inhibition of Wnt/β-catenin signaling. Transl Androl Urol 2016;5(Suppl 1):AB251. doi: 10.21037/tau.2016.s251

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