Matrix metalloproteinase 7 (MMP7), a metallohydrolase involved in the development of several cancers, is downregulated in the ApcMin/+ colon cancer mouse model following sulindac treatment. To determine whether this effect is relevant to the human condition, HT-29 human colon cancer cells were treated with sulindac and its metabolites, and compared to results obtained from in vivo mouse studies. The expression of MMP7 was monitored. The results demonstrated that sulindac sulfide effectively downregulated both MMP7 expression and activity. Furthermore, activity-based proteomics demonstrated that sulindac sulfide dramatically decreased the activity of leukotriene A4 hydrolase in HT-29 cells as reflected by a decrease in the level of its product, leukotriene B4. This study demonstrates that the effect of sulindac treatment in a mouse model of colon cancer may be relevant to the human counterpart and highlights the effect of sulindac treatment on metallohydrolases.
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机译:舒林酸治疗后,Apc Min / + sup>结肠癌小鼠模型中的基质金属蛋白酶7(MMP7)是一种参与多种癌症发展的金属水解酶。为了确定这种作用是否与人类状况有关,用舒林酸及其代谢产物处理了HT-29人类结肠癌细胞,并与从体内小鼠研究中获得的结果进行了比较。监测MMP7的表达。结果表明舒林酸硫化物有效地下调了MMP7的表达和活性。此外,基于活性的蛋白质组学表明,舒林酸硫化物显着降低了HT-29细胞中白三烯A4水解酶的活性,这反映为其产物白三烯B4含量的降低。这项研究表明舒林酸治疗结肠癌小鼠模型中的作用可能与人类模型有关,并强调了舒林酸治疗对金属水解酶的作用。
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