Jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition
Jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition
复制标题
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增殖和转移
DOI：
10.2147/dddt.s207315
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发表时间：
2019-01-01
影响因子：
4.8
通讯作者：
Sun, Yan-Fang
中科院分区：
文献类型：
--
作者：
Wang, Pan;Gao, Xiao-Yan;Sun, Yan-Fang
目的药根碱(JAT)是一种天然的原黄连素生物碱，具有解毒、杀菌、降血糖等活性。然而，其抗癌机制尚不清楚。本研究旨在探讨JAT在HCT-116和HT-29细胞中抑制结直肠癌的作用机制。方法采用四甲基偶氮唑盐比色法和集落形成法检测细胞增殖能力。Hoechst 33342染色和流式细胞仪分别检测细胞凋亡率和细胞周期。划痕愈合实验检测细胞迁移，Transwell-well实验检测细胞侵袭。进一步通过Western blotting检测相关蛋白的表达，并通过裸鼠移植瘤模型证实JAT的体内抗癌作用。结果JAT对Hct116和HT29细胞的增殖均有抑制作用，作用72 h的IC50值分别为6.75±0.29μM和5.29±0.13μM。并呈时间依赖性，细胞周期停滞于S期，促进细胞凋亡，抑制细胞迁移和侵袭。此外，JAT还通过减少β-连环蛋白和增加GSK-3β的表达来抑制Wnt信号通路。E-钙粘蛋白表达增加，N-钙粘蛋白表达降低，提示JAT抑制了细胞上皮-间充质转化(EMT)过程。在HCT-116裸鼠移植瘤模型中，JAT抑制肿瘤生长和转移，并诱导肿瘤细胞凋亡。结论JAT有效地抑制了结直肠癌细胞的生长和转移，为临床治疗结直肠癌提供了一个新的切入点。
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.