Saccharomyces boulardii inhibits EGF receptor signaling and intestinal tumor growth in Apc(min) mice.

Saccharomyces boulardii inhibits EGF receptor signaling and intestinal tumor growth in Apc(min) mice.
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DOI:
10.1053/j.gastro.2009.05.050
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发表时间:
2009-09
期刊:
影响因子:
29.4
通讯作者:
Kelly CP
Kelly CP
中科院分区:
医学1区
文献类型:
--
作者:
Chen X;Fruehauf J;Goldsmith JD;Xu H;Katchar KK;Koon HW;Zhao D;Kokkotou EG;Pothoulakis C;Kelly CP

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博拉迪酵母菌(Saccharomyces borlardii, Sb)是一种具有抗炎和抗菌活性的益生菌酵母菌,几十年来一直用于预防和治疗各种人类胃肠道疾病。我们之前报道过Sb通过下调Erk1/2 MAP激酶活性在体内和体外调节宿主炎症反应。本研究的目的是确定负责Erk1/2失活的上游介质,并检查Sb对ApcMin小鼠肿瘤发展的影响。我们发现,暴露于Sb后,EGF受体失活,导致EGFR-Erk和EGFR-Akt通路失活。在人结肠癌细胞中,Sb抑制EGF诱导的细胞增殖,减少细胞集落形成,促进细胞凋亡。Sb还能灭活HER-2、HER-3和IGF-1R。口服Sb可降低C57BL/6J Min/+ (ApcMin)小鼠的肠道肿瘤生长和发育不良。因此,除了具有抗炎作用外,博氏弧菌还能抑制EGFR和其他受体酪氨酸激酶信号传导,因此也可能在肠道肿瘤的治疗或预防中发挥新的作用。
Saccharomyces boulardii (Sb) is a probiotic yeast with anti-inflammatory and antimicrobial activities and has been used for decades in the prevention and treatment of a variety of human gastrointestinal disorders. We reported previously that Sb modulates host inflammatory responses through down regulation of Erk1/2 MAP kinase activities both in vitro and in vivo. The aim of this study was to identify upstream mediators responsible for Erk1/2 inactivation and to examine the effects of Sb on tumor development in ApcMin mice. We found that the EGF receptor was deactivated upon exposure to Sb leading to inactivation of both the EGFR-Erk and EGFR-Akt pathways. In human colonic cancer cells, Sb prevented EGF induced proliferation, reduced cell colony formation and promoted apoptosis. HER-2, HER-3 and IGF-1R were also found to be inactivated by Sb. Oral intake of Sb reduced intestinal tumor growth and dysplasia in C57BL/6J Min/+ (ApcMin) mice. Thus, in addition to its anti-inflammatory effects, S. boulardii inhibits EGFR and other receptor tyrosine kinase signaling and thereby may also serve a novel therapeutic or prophylactic role in intestinal neoplasia.
DOI: 10.1053/j.gastro.2006.10.001
发表时间: 2006-12-01
期刊: GASTROENTEROLOGY
影响因子: 29.4
作者:
Dalmasso, Guillaume;Cottrez, Francoise;Groux, Herve
通讯作者: Groux, Herve
DOI: 10.1016/0016-5085(93)90280-p
发表时间: 1993-04-01
期刊: GASTROENTEROLOGY
影响因子: 29.4
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发表时间: 2007-11-28
影响因子: 4.3
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通讯作者: Gil-Bazo, I.
DOI: 10.1007/bf01536771
发表时间: 1990-02-01
影响因子: 3.1
作者:
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