期刊
POSTEPY HIGIENY I MEDYCYNY DOSWIADCZALNEJ
卷 74, 期 -, 页码 224-235出版社
POLISH ACAD SCIENCES, INST IMMUNOL & EXP THERAPY
DOI: 10.5604/01.3001.0014.2497
关键词
canonical Wnt signaling; colorectal cancer; Porcupine; CBP
Aim: The activation of canonical Wnt pathway is etiologically associated with the development of colorectal cancers. There are many possible molecular targets for the therapeutic abrogation of Wnt/beta-catenin signaling. The aim of this study was to select the best molecular targets for the attenuation of beta-catenin-dependent gene expression in colorectal cancer cell lines. Material/Methods: An siRNA screen was used for the selection of the best molecular targets for the down-regulation of TCF/LEF-dependent GFP expression in HCT116 cells. The level of the expression of beta-catenin target genes was analyzed by qPCR.The effect of the tested chemicals on cell migration, cell cycle and apoptosis was assessed by the wound healing assay, flow cytometric analysis of propidium iodide stained cells and flow cytometric analysis of the activity of caspases-3/7, respectively. Results: Of the forty three genes which were tested in the screening stage, eight (KDM6A, KDM1A, PORCN, KDM4C, CARM1, DVL1, CBP, KMT2A) were selected as most promising. Small molecule inhibitors of these proteins (GSK-J4, GSK-LSD1, IWP-2, ML324, MS049, Dvl-PDZ Domain Inhibitor II, PRI-724, MM-102) were further used. The inhibitors of Porcupine (IWP-2) and CBP (PRI-724) were most effective in the down-regulation of the expression of beta-catenin target genes and the induction of apoptosis in HCT116 cells, but showed weaker effects in DLD-1 cells. Conclusions: The inhibition of CBP and Porcupine is the most effective in attenuating canonical Wnt signaling in colon cancer cells. Future studies should determine which factors affect the sensitivity towards these promising anti-cancer agents.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据