首頁> 外文期刊>Biochimica et Biophysica Acta. Molecular and cell biology of Lipids >Molecular and cellular effects of cis-9, trans-11-conjugated linoleic acid in enterocytes: Effects on proliferation, differentiation, and gene expression
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Molecular and cellular effects of cis-9, trans-11-conjugated linoleic acid in enterocytes: Effects on proliferation, differentiation, and gene expression

機譯:順式9,反式11共軛亞油酸在腸細胞中的分子和細胞效應:對增殖,分化和基因表達的影響

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It has been hypothesized that dietary conjugated linoleic acids (CLA) May inhibit colon tumorigenesis. The aim of our study was to investigate the cellular and molecular effects of cis-9 (9Z), trans-11 (11E)-CLA on the proliferation, differentiation, interaction with peroxisome proliferator-activated receptors (PPARs), and expression of genes relevant in the APC-beta-catenin-TCF4 signalling pathway in human HT-29 and Caco-2 colon cells. We found that 9Z,11E-CLA inhibited the proliferation of HT-29 and Caco-2 cells. Transvaccenic acid (VA) showed no antiproliferative effects at all. We determined that 9Z,11E-CLA induced cell differentiation as measured by intestinal alkaline phosphatase (IAP) enzyme activity in Caco-2 cells, mRNA expression of IAP, and activation of a 5' flanking region of IAP. The 9Z,11E-CLA activated human PPAR delta as measured in a reporter gene assay. Treatment of HT29 cells in the poliferation phase with 9Z,11E-CLA repressed mRNA-expression of proliferation genes such as c-myc, cyclin D1 and c-jun in a concentration dependent manner. The promoter activities of c-myc and AP1 were also inhibited after incubation with 9Z,11E-CLA. beta-Catenin mRNA and protein expression was also repressed by the treatment with 9Z,11E-CLA. In addition, the mRNA expression of PPAR6 was repressed by treatment of the HT-29 cells with 9Z,11E-CLA. We conclude that 9Z,11E-CLA has an antiprolifierative effect at the cellular and molecular levels in human colon cells. The results indicate that the preventive effects of CLA in the development of colon cancer may be due to their downregulation of some target-genes of the APC-beta-catemn-TCF-4-. and PPAR6 signalling pathway. (c) 2005 Elsevier B.V. All rights reserved.
機譯:假設飲食中的共軛亞油酸(CLA)可能會抑制結腸腫瘤的發生。本研究的目的是研究cis-9(9Z),trans-11(11E)-CLA對細胞的增殖,分化,與過氧化物酶體增殖物激活受體(PPAR)相互作用和基因表達的細胞和分子影響與人HT-29和Caco-2結腸細胞中的APC-β-catenin-TCF4信號通路相關。我們發現9Z,11E-CLA抑制HT-29和Caco-2細胞的增殖。 Transvaccenic酸(VA)完全沒有顯示抗增殖作用。我們確定9Z,11E-CLA可以通過Caco-2細胞中的腸堿性磷酸酶(IAP)酶活性,IAP的mRNA表達以及IAP的5'側翼區域的活化來誘導細胞分化。 9Z,11E-CLA激活的人PPARδ,在報道基因分析中測得。用9Z,11E-CLA在增殖期處理HT29細胞以濃度依賴的方式抑制了增殖基因如c-myc,cyclin D1和c-jun的mRNA表達。與9Z,11E-CLA孵育后,c-myc和AP1的啟動子活性也受到抑制。用9Z,11E-CLA處理也可抑制β-CateninmRNA和蛋白質的表達。另外,通過用9Z,11E-CLA處理HT-29細胞來抑制PPAR6的mRNA表達。我們得出的結論是9Z,11E-CLA在人結腸細胞的細胞和分子水平上具有抗增殖作用。結果表明,CLA在結腸癌發展中的預防作用可能是由于它們下調了APC-beta-catemn-TCF-4-的某些靶基因。和PPAR6信號通路。 (c)2005 Elsevier B.V.保留所有權利。

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