<p>Jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through Wnt/β-catenin signaling pathway and epithelial–mesenchymal transition</p>

Abstract

Purpose Jatrorrhizine (JAT) is a natural protoberberine alkaloid, possesses detoxification, bactericidal and hypoglycemic activities. However, its anti-cancer mechanism is not clear. This study aimed to investigate the mechanism of JAT through which inhibits colorectal cancer in HCT-116 and HT-29 cells. Methods MTT assay and colony formation assay were used to check the cell proliferation ability. Cell apoptosis and cell cycle were measured by Hoechst 33342 staining and flow cytometry, respectively. Cell migration and invasion were detected by scratch wound healing assay and trans-well assay, respectively. Further, expression of related proteins was examined via Western blotting and the in vivo anti-cancer effect of JAT was confirmed by nude mice xenograft model. Results The research showed that JAT inhibited the proliferation of HCT-116 and HT-29 cells with IC 50 values of 6.75±0.29 μM and 5.29±0.13 μM, respectively, for 72 hrs. It has also showed a time dependently, cell cycle arrested in S phase, promoted cell apoptosis and suppressed cell migration and invasion. In addition, JAT inhibited Wnt signaling pathway by reducing β-catenin and increasing GSK-3β expressions. Increased expression of E-cadherin, while decreased N-cadherin, indicating that JAT treatment suppressed the process of cell epithelial–mesenchymal transition (EMT). In HCT-116 nude mice xenograft model, JAT inhibited tumor growth and metastasis, and induced apoptosis of tumor cells. Conclusion This study demonstrated that JAT efficiently inhibited colorectal cancer cells growth and metastasis, which provides a new point for clinical treatment of colorectal cancer.

DNER promotes epithelial–mesenchymal transition and prevents chemosensitivity through the Wnt/β-catenin pathway in breast cancer

“…The effect of β-catenin and EMT on cell apoptosis has been reported 34 , 35 , but the role of DNER in epirubicin-induced apoptosis has not been studied. DNER and β-catenin were expressed in an epirubicin concentration-dependent manner.…”

MicroRNA‑325‑3p contributes to colorectal carcinoma by targeting cytokeratin 18

“…In addition, CK18 was identified as a target gene of miR-325-3p, suggesting that miR-325-3p is associated with the degree of EMT in CRC. EMT is widely involved in the invasion and metastasis of colon cancer due to the loss of epithelial characteristics into mesenchymal cells ( 24 , 25 ). The results of the present study demonstrated that high miR-325-3p expression significantly decreased the expression of the epithelial marker, CK18, but increased the expression levels of the mesenchymal markers, vimentin and α-SMA.…”

Astragalus polysaccharide inhibits breast cancer cell migration and invasion by regulating epithelial‑mesenchymal transition via the Wnt/β‑catenin signaling pathway

“…APS inhibits EMT by suppressing the activity of the Wnt/β-catenin signaling pathway. The Wnt signaling pathway is an important classical pathway in eMT (17). The present study investigated whether aPS exerted its antitumor effect by suppressing the activity of the Wnt/β-catenin signaling pathway.…”

“…Previous studies demonstrated that a variety of factors can induce eMT, including transforming growth factor β (TGF-β), Wnt, Notch and fibroblast growth factor (13)(14)(15)(16). among these inducers, the Wnt/β-catenin signaling pathway, which can be divided into classical and non-classical signaling pathways, has attracted increasing attention (17). Wnt has been identified as the promoter of the pathway (18) and, as an upstream factor, β-catenin affects the expression of downstream factors of the signaling pathway, including c-Myc and cyclin d1 (19).…”