The synthetic triterpenoids CDDO-methyl ester and CDDO-ethyl amide prevent lung cancer induced by vinyl carbamate in A/J mice
The synthetic triterpenoids CDDO-methyl ester and CDDO-ethyl amide prevent lung cancer induced by vinyl carbamate in A/J mice
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DOI：
10.1158/0008-5472.can-06-4534
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发表时间：
2007-03-15
期刊：
影响因子：
11.2
通讯作者：
Sporn, Michael B.
中科院分区：
文献类型：
--
作者：
Liby, Karen;Royce, Darlene B.;Sporn, Michael B.
我们报告了首次使用新的合成三萜类化合物来预防实验动物肺癌。雌性A/J小鼠用致突变致癌物氨基甲酸乙烯酯处理，其在16周内诱导所有动物的肺腺癌。如果小鼠在给药致癌物后1周开始喂食合成三萜2-氰基-3，12-二氧代齐墩果烷-1，9（11）-二烯-28-酸的甲酯或乙酰胺衍生物（分别为CDDO-ME和CDDO-EA），肺癌的数量、大小和严重程度显著降低。与这些体内发现密切相关的CDDO-ME和CDDO-EA的作用机制是此处在细胞培养中显示的以下结果：（a）在巨噬细胞样细胞系RAW 264.7中抑制IFN-γ诱导一氧化氮合酶从头形成的能力，（B）在这些RAW细胞中诱导血红素加氧酶-1，和（c）抑制人肺癌细胞系中转录因子信号转导子和转录激活子3的磷酸化以及诱导细胞凋亡。
We report the first use of new synthetic triterpenoids to prevent lung cancer in experimental animals. Female A/J mice were treated with the mutagenic carcinogen vinyl carbamate, which induces adenocarcinoma of the lung in all animals within 16 weeks. If mice were fed either the methyl ester or the ethyl amide derivative of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-ME and CDDO-EA, respectively), beginning I week after dosing with carcinogen, the number, size, and severity of lung carcinomas were markedly reduced. The mechanisms of action of CDDO-ME and CDDO-EA that are germane to these in vivo findings are the following results shown here in cell culture: (a) suppression of the ability of IFN-gamma to induce de novo formation of nitric oxide synthase in a macrophage-like cell line RAW264.7, (b) induction of heme oxygenase-1 in these RAW cells, and (c) suppression of phosphorylation of the transcription factor signal transducers and activators of transcription 3 as well as induction of apoptosis in human lung cancer cell lines.