NADPH oxidase overexpression in human colon cancers and rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).
NADPH oxidase overexpression in human colon cancers and rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).
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DOI：
10.1002/ijc.25610
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发表时间：
2011-06-01
影响因子：
6.4
通讯作者：
Dashwood, Roderick H.
中科院分区：
文献类型：
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作者：
Wang, Rong;Dashwood, Wan-Mohaiza;Nian, Hui;Loehr, Christiane V.;Fischer, Kay A.;Tsuchiya, Naoto;Nakagama, Hitoshi;Ashktorab, Hassan;Dashwood, Roderick H.
NADPH氧化酶/双氧化酶（Nox/Duox）家族成员与核因子κ-B（NFκB）介导的炎症和炎症相关病理学有关。我们首次尝试检测Nox/Duox和NFκB在用熟肉杂环胺致癌物2-氨基-1-甲基-6-苯基咪唑[4，5-B]吡啶（PhIP）处理的大鼠中的作用。在1年后的PhIP诱导的结肠肿瘤中，Nox 1、Nox 4、NFκB-p50和NFκB-p65均高度过表达，与邻近正常结肠粘膜相比。与其匹配的对照组相比，一组原发性人类结肠癌中Nox 1和Nox 4 mRNA和蛋白水平也显著升高。在HT 29人结肠癌细胞中，Nox 1敲低诱导G1细胞周期停滞，而在Caco-2细胞中有强烈的凋亡反应，裂解的caspase-3，-6，-7和聚（ADP-核糖）聚合酶水平增加。Nox 1敲低阻断脂多糖诱导的IκB激酶磷酸化，抑制NFκB（p50和p65）蛋白的核转位，并减弱NFκB DNA结合活性。下游NFκB靶点如MYC、CCND 1和IL 1 β的表达相应减少。这些结果为Nox 1、Nox 4和NFκB在PhIP诱导的结肠癌发生中的作用提供了第一个证据，包括在肿瘤发生前的早期阶段。总的来说，这项研究和其他研究的结果表明，Nox/Duox家族成员和NFκB在结肠癌发展中的作用需要进一步研究。
NADPH oxidase/dual-oxidase (Nox/Duox) family members have been implicated in nuclear factor kappa-B (NFκB)-mediated inflammation and inflammation-associated pathologies. We sought to examine, for the first time, the role of Nox/Duox and NFκB in rats treated with the cooked meat heterocyclic amine carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). In the PhIP-induced colon tumors obtained after 1 year, Nox1, Nox4, NFκB-p50 and NFκB-p65 were all highly overexpressed compared with their levels in adjacent normal-looking colonic mucosa. Nox1 and Nox4 mRNA and protein levels also were markedly elevated in a panel of primary human colon cancers, compared with their matched controls. In HT29 human colon cancer cells, Nox1 knockdown induced G1 cell cycle arrest, whereas in Caco-2 cells there was a strong apoptotic response, with increased levels of cleaved caspase-3, -6, -7 and poly(ADP-ribose)polymerase. Nox1 knockdown blocked lipopolysaccharide-induced phosphorylation of IκB kinase, inhibited the nuclear translocation of NFκB (p50 and p65) proteins, and attenuated NFκB DNA binding activity. There was a corresponding reduction in the expression of downstream NFκB targets, such as MYC, CCND1 and IL1β. The results provide the first evidence for a role of Nox1, Nox4 and NFκB in PhIP-induced colon carcinogenesis, including during the early stages before tumor onset. Collectively, the findings from this investigation and others suggest that further work is warranted on the role of Nox/Duox family members and NFκB in colon cancer development.
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影响因子：
3.6
作者：
Desouki, MM;Kulawiec, M;Singh, KK
通讯作者：
Singh, KK
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
2.8
作者：
Lim, SD;Sun, C;Arnold, RS
通讯作者：
Arnold, RS
影响因子：
4.8
作者：
Anrather, J;Racchumi, G;Iadecola, C
通讯作者：
Iadecola, C
DOI：
10.1016/s0027-5107(02)00155-0
发表时间：
2002-09-30
影响因子：
2.3
作者：
Gooderham, NJ;Zhu, H;Creton, S
通讯作者：
Creton, S