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

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 beta-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 beta-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 timedependent manner. Moreover, berberine induced the translocation of beta-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.

Automated summary

This study revealed that berberine can inhibit the proliferation of colon cancer cells by regulating the β-catenin signaling pathway. The expression level of CTNNB1, the active component of berberine, was found to be higher in colon cancer patients compared to normal controls. This suggests that CTNNB1 may have potential clinical diagnostic and therapeutic value in colon cancer.