Serfaty L, Bissonnette M, Poupon R
Service d'hépatologie, hôpital Saint-Antoine, Assistance publique-Hôpitaux de Paris, université Pierre-et-Marie-Curie, 184 rue du Faubourg-Saint-Antoine, Paris cedex 12, France.
Gastroenterol Clin Biol. 2010 Oct;34(10):516-22. doi: 10.1016/j.gcb.2010.05.005. Epub 2010 Jul 6.
Colorectal cancer is respectively the third and second most common cancer among men and women in France. Interest in chemoprevention for colorectal cancer has increased over the last two decades. Beside non-steroidal anti-inflammatory drugs, ursodeoxycholic acid (UDCA) may have chemopreventive action in colorectal cancer with a likely better tolerance. In high-risk populations such as patients with inflammatory bowel disease or prior colorectal adenoma or carcinoma, retrospective and prospective studies have suggested a beneficial effect of UDCA. In azoxymethane model, UDCA inhibits tumor development by countering the tumor-promoting effects of secondary bile acids, such as deoxycholic acid (DCA). The opposing effects of UDCA and DCA on lipid raft composition may be central to their effects on colonic tumorigenesis. Differential effects of DCA and UDCA on growth factor and inflammatory signals involved in colorectal carcinogenesis, such as epidermal growth factor receptors (EGFR) signaling and Cox-2 expression, likely mediate their opposing effects on colonic tumor promotion and tumor inhibition, respectively.
在法国,结直肠癌分别是男性和女性中第三和第二常见的癌症。在过去二十年中,对结直肠癌化学预防的关注有所增加。除了非甾体抗炎药外,熊去氧胆酸(UDCA)可能对结直肠癌具有化学预防作用,且耐受性可能更好。在炎症性肠病患者、既往有结直肠腺瘤或癌的患者等高风险人群中,回顾性和前瞻性研究均提示了UDCA的有益作用。在氧化偶氮甲烷模型中,UDCA通过对抗次级胆汁酸(如脱氧胆酸,DCA)的促肿瘤作用来抑制肿瘤发展。UDCA和DCA对脂筏组成的相反作用可能是它们对结肠肿瘤发生作用的核心。DCA和UDCA对结直肠癌发生过程中涉及的生长因子和炎症信号(如表皮生长因子受体(EGFR)信号传导和Cox-2表达)的不同作用,可能分别介导了它们对结肠肿瘤促进和肿瘤抑制的相反作用。