论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
药根碱通过 Wnt/β-catenin 信号通路和上皮 - 间质转化抑制结直肠癌的增殖和转移
Authors Wang P, Gao XY, Yang SQ, Sun ZX, Dian LL, Qasim M, Phyo AT, Liang ZS, Sun YF
Received 1 March 2019
Accepted for publication 21 May 2019
Published 8 July 2019 Volume 2019:13 Pages 2235—2247
DOI https://doi.org/10.2147/DDDT.S207315
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 2
Editor who approved publication: Dr Qiongyu Guo
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 IC50 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.
Keywords: jatrorrhizine (JAT), colorectal cancer (CRC), Wnt/β-catenin signaling, epithelial-mesenchymal transition (EMT), xenograft model