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Novel Peptide Inhibitors of β-Catenin Effectively Suppress the Tumorigenesis of Colorectal Cancer

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Abstract

Aberrant β-catenin activation promotes the proliferation and survival of several types of tumor cells, including colorectal cancer (CRC) cells. Synthetic peptides are drug candidates for treating various diseases; however, peptide inhibitors of β-catenin have been rarely reported. A series of peptide inhibitors for β-catenin (F15A1–9k, F15A2–9k, and F15A3–9k) were designed and synthesized, and then used to treat human CRC cells (HT-29). Next, a series of in vitro assays, including cell counting, colony formation, flow cytometry, and Transwell assays, were performed to assess the biological effects of the peptides on CRC cells. Mouse xenograft models of HT-29 tumors were also used to evaluate the inhibitory effect of the peptide inhibitors on β-catenin expression in vivo. The inhibitory effect of the peptide inhibitors on β-catenin production was tested in a confocal laser scanning microscope study (CLSMS), and by H&E, TUNEL, and immunohistochemical (IHC) staining. The peptide inhibitors significantly reduced the viability of HT-29 cells in time- and concentration-dependent manners. Moreover, the peptide inhibitors for β-catenin significantly inhibited CRC tumorigenesis both in vitro and in vivo. Mechanistically, the peptide inhibitors for β-catenin inhibited the angiogenesis activity of HT-29 cells. When administered by itself, F15A2–9k blocked cell division, induced apoptosis, and reduced the migration and invasion capabilities of HT-29 cells, while a combination of F15A1–9k, F15A2–9k, and F15A3–9k showed even stronger inhibitory effects on HT-29 cells. In summary, the peptides designed to inhibit β-catenin demonstrated anti-tumor activity both in vitro and in vivo, suggesting their potential as therapeutic agents for treating CRC.

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Acknowledgements

This study was supported by grant from Basic Medical College of Shanxi Medical University (No. 20-1207).

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Author notes

  1. Honglin Liu and Xingyun Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China

    Honglin Liu, Xia Zhou, Xiutao Tan & Niuliang Cheng

  2. Department of Clinical Medicine, Fujian Medical University, Fuzhou, China

    Xingyun Liu

  3. Department of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot, China

    Yuexi Li

  4. Department of Biotechnology, Capital of Institute of Pediatrics, Beijing, China

    Bo Niu

  5. Department of Medical Oncology, The Third People’s Hospital of Datong, No. 1 Wenchang Street, Datong, 037008, Shanxi Province, China

    Hailin Liu

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  1. Honglin Liu
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  4. Xia Zhou
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Correspondence to Hailin Liu.

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Liu, H., Liu, X., Li, Y. et al. Novel Peptide Inhibitors of β-Catenin Effectively Suppress the Tumorigenesis of Colorectal Cancer. Int J Pept Res Ther 27, 263–274 (2021). https://doi.org/10.1007/s10989-020-10080-0

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  • DOI: https://doi.org/10.1007/s10989-020-10080-0

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