5-Aminosalicylic acid inhibits stem cell function in human adenoma-derived cells: implications for chemoprophylaxis in colorectal tumorigenesis.
5-Aminosalicylic acid inhibits stem cell function in human adenoma-derived cells: implications for chemoprophylaxis in colorectal tumorigenesis.
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DOI：
10.1038/s41416-021-01354-5
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发表时间：
2021-06
影响因子：
8.8
通讯作者：
Williams AC
中科院分区：
文献类型：
--
作者：
Dixon SW;Collard TJ;Mortensson EMH;Legge DN;Chambers AC;Greenhough A;Creed TJ;Williams AC
大多数结直肠癌（CRC）零星地起源于前驱病变：结肠息肉。息肉切除可防止进展为结直肠癌。未来发生息肉的风险与筛查中发现的息肉的数量和大小成正比，从而确定可能受益于有效化学预防的高危个体。我们的目的是研究5-氨基水杨酸（5-ASA），一种用于治疗溃疡性结肠炎的药物，作为散发性结直肠癌的可能预防剂的潜力。用5-ASA处理人结直肠腺瘤（PC/AA/C1、S/AN/C1和S/RG/C2）、转化腺瘤PC/AA/C1/SB10和癌细胞（LS174T和SW620）。研究了β-catenin对二维和三维（3D）培养细胞生长、β-catenin转录活性和肿瘤干细胞特性的影响。体外实验显示，5-ASA能抑制腺瘤细胞的生长，抑制β-catenin的转录活性。利用肿瘤发生的3D模型发现，下调β-catenin可抑制干细胞标志物LGR5（富亮氨酸G蛋白偶联受体-5）的表达，并在功能上抑制人腺瘤和癌细胞的干性。5-ASA可抑制腺瘤源性细胞的癌干表型。价格合理且耐受性良好的5-ASA是降低高危人群结肠直肠息肉和结直肠癌风险的一种化学预防药物。
Most colorectal cancers (CRC) arise sporadically from precursor lesions: colonic polyps. Polyp resection prevents progression to CRC. Risk of future polyps is proportional to the number and size of polyps detected at screening, allowing identification of high-risk individuals who may benefit from effective chemoprophylaxis. We aimed to investigate the potential of 5-aminosalicylic acid (5-ASA), a medication used in the treatment of ulcerative colitis, as a possible preventative agent for sporadic CRC. Human colorectal adenoma (PC/AA/C1, S/AN/C1 and S/RG/C2), transformed adenoma PC/AA/C1/SB10 and carcinoma cell lines (LS174T and SW620) were treated with 5-ASA. The effect on growth in two- and three-dimensional (3D) culture, β-catenin transcriptional activity and on cancer stemness properties of the cells were investigated. 5-ASA was shown, in vitro, to inhibit the growth of adenoma cells and suppress β-catenin transcriptional activity. Downregulation of β-catenin was found to repress expression of stem cell marker LGR5 (leucine-rich G protein-coupled receptor-5) and functionally suppress stemness in human adenoma and carcinoma cells using 3D models of tumorigenesis. 5-ASA can suppress the cancer stem phenotype in adenoma-derived cells. Affordable and well-tolerated, 5-ASA is an outstanding candidate as a chemoprophylactic medication to reduce the risk of colorectal polyps and CRC in those at high risk.
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影响因子：
168.9
作者：
Burn, John;Gerdes, Anne-Marie;Macrae, Finlay;Mecklin, Jukka-Pekka;Moeslein, Gabriela;Olschwang, Sylviane;Eccles, Diane;Evans, D. Gareth;Maher, Eamonn R.;Bertario, Lucio;Bisgaard, Marie-Luise;Dunlop, Malcolm G.;Ho, Judy W. C.;Hodgson, Shirley V.;Lindblom, Annika;Lubinski, Jan;Morrison, Patrick J.;Murday, Victoria;Ramesar, Raj;Side, Lucy;Scott, Rodney J.;Thomas, Huw J. W.;Vasen, Hans F.;Barker, Gail;Crawford, Gillian;Elliott, Faye;Movahedi, Mohammad;Pylvanainen, Kirsi;Wijnen, Juul T.;Fodde, Riccardo;Lynch, Henry T.;Mathers, John C.;Bishop, D. Timothy
通讯作者：
Bishop, D. Timothy
影响因子：
10.5
作者：
de Lau W;Peng WC;Gros P;Clevers H
通讯作者：
Clevers H
影响因子：
24.5
作者：
Baan, Bart;Dihal, Ashwin A.;van den Brink, Gijs R.
通讯作者：
van den Brink, Gijs R.
影响因子：
29.4
作者：
Logan, Richard F. A.;Grainge, Matfhew J.;Muir, Kenneth R.
通讯作者：
Muir, Kenneth R.
影响因子：
4.9
作者：
Koelink, Pim J.;Mieremet-Ooms, Marij A. C.;Verspaget, Hein W.
通讯作者：
Verspaget, Hein W.