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Effect of endostatin on Wnt pathway of stem-like cells in bladder cancer in tumor microenvironment

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Abstract

Wnt/β-catenin signaling pathway modulates miscellaneous biological events in cells including gene expression, cell growth, apoptosis, metabolism and transition. The aim of this study was to investigate the effect of endostatin on Wnt signaling pathway of stem-like cells in bladder cancer in tumor microenvironment. The qRT-PCR assay and western blot were conducted to evaluate related factors expressions of Wnt signaling pathway in both bladder cancer 5637 cells and stem cells. Loss of function assays were carried out to detect the influence of endostatin on the proliferation, migration, cell proliferation and apoptosis of bladder cancer cells. We demonstrated that endostatin triggered the degradation of β-catenin, a key mediator of Wnt signaling. The activation of the endostatin blocked β-catenin function and inhibited cell growth and migration of bladder cancer. In order to verify that the Wnt/β-catenin signaling pathway was inhibited by endostain in 5637 bladder cancer cells and stem cells, the Wnt/β-catenin signaling pathway-associated molecules, including DKK1, LRP5, TCF4, β-catenin, cyclin D1, and c-Myc, were evaluated in 5637 bladder cancer cells and stem cells. The western blotting results showed that expressions of these molecules were remarkably increased in the 5637 bladder cancer cells and stem cells compared to the control group. In summary, our study demonstrated that endostatin inhibited angiogenesis. The downregulation of the Wnt/β-catenin pathway may be engaged in the suppression of angiogenesis by endostatin in bladder cancer cells and cancer stem cells.

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Funding

This work was supported by City of Nanchong Strategic Cooperation with Local Universities Foundation of Technology (NSMC20170421, NSMC20170111, 18SXHZ0581, 18SXHZ0128).

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Author notes

  1. Tao Wu and Xi Duan have contributed equally to this study.

Authors and Affiliations

  1. Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People’s Republic of China

    Tao Wu, Tinghui Hu, Xiaoxi Mu, Guo Jiang & Shu Cui

  2. Department of Dermatovenereology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China

    Xi Duan

Authors
  1. Tao Wu
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  2. Xi Duan
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  3. Tinghui Hu
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  4. Xiaoxi Mu
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  5. Guo Jiang
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  6. Shu Cui
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Correspondence to Shu Cui.

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Wu, T., Duan, X., Hu, T. et al. Effect of endostatin on Wnt pathway of stem-like cells in bladder cancer in tumor microenvironment. Mol Biol Rep 47, 3937–3948 (2020). https://doi.org/10.1007/s11033-020-05487-3

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  • DOI: https://doi.org/10.1007/s11033-020-05487-3

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