Heliyon (Jan 2024)
Berberine improved the microbiota in lung tissue of colon cancer and reversed the bronchial epithelial cell changes caused by cancer cells
Abstract
Objective: The lung is a common organ for colon cancer metastasis, and the objective of this experiment was to explore the protective effect of berberine on lung tissue or alveolar epithelial cells induced by colon cancer. Methods: Thirty-six BALB/c nude mice were used to establish a xenograft model of colon cancer with the HT29 cell line and were treated with berberine and probiotics. Human bronchial epithelial BEAS-2B cells were induced by conditioned medium (CM) from the colon cancer cell lines HT29 and RKO and were treated with berberine. Lung tissues were collected to detect the changes in the microbiota using 16S rDNA sequencing and the expression of inflammatory cytokines. The expression of E-cadherin and N-cadherin in BEAS-2B cells was detected by cellular immunofluorescence. The changes in cell proliferation were detected by the CCK-8 assay. Western blotting was used to detect E-cadherin, N-cadherin, collagen I, fibronectin, PDGF-β, and RAD51 expression in BEAS-2B cells. Results: The richness and evenness of the microbiota in the lung tissues of mice with colon cancer were significantly lower than those of the control group. Berberine significantly increased the abundances of Bacteroidetes, Bacteroidia, Bacteroidales, Lactobacillaceae, Lactobacillus and Acinetobacter in the lung tissue of mice with colon cancer, with reduced abundances of Actinobacteria, Bacillales, Staphylococcaceae and Staphylococcus. Berberine or probiotics significantly increased the alpha diversity of the lung microbiota. Compared with probiotics, berberine significantly enhanced the abundance of microbiota involved in the metabolism of lysosomes, flavone and flavonol biosynthesis, glycosaminoglycan degradation, and glycosphingolipid biosynthesis-ganglio. Berberine increased IL-6 and IL-10 and decreased IL-17 and IFN-γ expression in lung tissue (P > 0.05), but berberine-probiotics significantly decreased IL-17 and IFN-γ and increased IL-10 expression (P < 0.05). Colon cancer cells could not induce BEAS-2B proliferation but decreased the expression of the epithelial marker E-cadherin and altered the expression of extracellular matrix-related proteins (collagen I, fibronectin, and PDGF-β), which were reversed by berberine. Berberine increased RAD51 expression in BEAS-2B cells, which had been decreased by HT29 and RKO CM treatment. Conclusion: Berberine can selectively regulate the abundance of some microbiomes of lung tissue in colon cancer, improve the inflammatory response in lung tissue, and antagonize the cancerous stimulation of colon cancer cells to lung tissue cells by regulating the bronchial epithelial cell phenotype, extracellular matrix remodelling and the expression of the repair gene RAD51.
