Selective Wnt/β-catenin Small-molecule Inhibitor CWP232228 Impairs Tumor Growth of Colon Cancer
Selective Wnt/β-catenin Small-molecule Inhibitor CWP232228 Impairs Tumor Growth of Colon Cancer
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DOI：
10.21873/anticanres.13514
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发表时间：
2019-07-01
影响因子：
2
通讯作者：
Chun, Kyung-Soo
中科院分区：
文献类型：
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作者：
Kim, Jin Young;Park, Geumi;Chun, Kyung-Soo
背景/目的：探讨选择性小分子β-连环蛋白抑制剂CWP232228作为治疗结直肠癌(CRC)的潜在药物的可能性。材料和方法：采用流式细胞仪、免疫印迹和荧光素酶报告等方法分析CWP2228对体外培养的HCT116细胞的作用。NOD-SCID IL2RGamma(Null)小鼠用于体内异种移植研究，以验证体外研究。结果：CWP232228作用于HCT116细胞后，β-连环蛋白启动子活性和核表达均下降，并诱导出明显的细胞毒作用。CWP232228诱导细胞凋亡，细胞周期停滞于细胞周期的G(1)期。此外，CWP232228还可降低极光激酶A、c-Myc、细胞周期蛋白D1和小眼球相关转录因子的表达。最后，CWP232228还能抑制小鼠移植的结肠癌细胞的生长。结论：CWP232228可作为治疗结直肠癌的潜在药物。
Background/Aim: To explore the possibility of a selective small-molecule beta-catenin inhibitor, CWP232228, as a potential therapeutic drug in the treatment of colorectal cancer (CRC). Materials and Methods: The effect of CWP2228 on HCT116 cells was analysed in vitro via flow cytometry, western immunoblotting, and luciferase reporter assays. NOD-scid IL2Rgamma(null) mice were employed for an in vivo xenograft study to validate the in vitro studies. Results: CWP232228 treatment decreased the promoter activity and nuclear expression of beta-catenin and induced a significant cytotoxic effect in HCT116 cells. CWP232228 treatment induced apoptosis and cell-cycle arrest in the G(1) phase of the cell cycle. Furthermore, CWP232228 decreased the expression of aurora kinase A, c-Myc, cyclin D1 and microphthalmia-associated transcription factor. Lastly, CWP232228 also inhibited the growth of xenografted colon cancer cells in mice. Conclusion: Collectively, CWP232228 may be used as a potential therapeutic drug in CRC.