β-catenin correlates with the progression of colon cancers and berberine inhibits the proliferation of colon cancer cells by regulating the β-catenin signaling pathway.

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  • Additional Information
    • Source:
      Publisher: Elsevier/North-Holland Country of Publication: Netherlands NLM ID: 7706761 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0038 (Electronic) Linking ISSN: 03781119 NLM ISO Abbreviation: Gene Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam, Elsevier/North-Holland, 1976-
    • Subject Terms:
      Disease Progression* ; Signal Transduction*/drug effects; Berberine/*therapeutic use ; Colonic Neoplasms/*drug therapy ; Colonic Neoplasms/*pathology ; beta Catenin/*metabolism; Aged ; Animals ; Berberine/pharmacology ; Case-Control Studies ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Colonic Neoplasms/genetics ; DNA Methylation/drug effects ; DNA Methylation/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Male ; Mice, Inbred C57BL ; Middle Aged ; Multivariate Analysis ; Promoter Regions, Genetic/genetics ; Proportional Hazards Models ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Time Factors ; beta Catenin/genetics ; Mice
    • Abstract:
      Introduction: Berberine was one of the active components in Chinese herb and exerted tumor suppressive role in cancer progression, but the exact antitumor mechanism is still not clearly clarified. In the present study, bioinformatics analysis was performed on COAD patients from TCGA, HPA database, UALCAN and GEPIA 2 platform. We also explored the role of berberine on progression of human colon cancers in vitro and in vivo and clarified weather the antitumor effects of berberine was mediated by Wnt/beta-catenin pathway.
      Methods: Cell viability was determined by MTT assay. The protein levels were tested by western blotting and the distribution of β-catenin was observed by confocal microscope.
      Results: The results showed the levels of CTNNB1 mRNA was increased in colon cancer patients than normal controls. The diagnostic value of CTNNB1 was AUC = 0.882 (CI:0.854-0.911) with sensitivity of 1.000 and specificity of 0.777. The promoter methylation level of CTNNB1 in COAD patients was significantly decreased. Moreover, univariate analysis and multivariate analysis results showed the expression of CTNNB1 in COAD patients was associated with T stage (p = 0.010), pathological stage (p = 0.025) and perineural invasion (p = 0.025). Furthermore, the in vitro assay results showed β-catenin signaling was highly activated in human colon cancer cells and berberine inhibited the cell viability of colon cancer cells in vitro and in vivo in a dose-and time-dependent manner. Moreover, berberine induced the translocation of β-catenin to cytoplasm from nucleus.
      Conclusion: The levels of CTNNB1 mRNA was increased in colon cancer patients than normal controls. Berberine inhibited the proliferation of colon cancer cells by regulating the beta-catenin signaling pathway.
      (Copyright © 2022 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Berberine; Colon cancer; Translocation; Wnt/β-catenin
    • Accession Number:
      0 (RNA, Messenger)
      0 (beta Catenin)
      0I8Y3P32UF (Berberine)
    • Publication Date:
      Date Created: 20220122 Date Completed: 20220301 Latest Revision: 20240226
    • Publication Date:
      20240226
    • Accession Number:
      10.1016/j.gene.2022.146207
    • Accession Number:
      35063579