4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes esophageal squamous cell carcinoma growth via beta-adrenoceptors in vitro and in vivo.
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes esophageal squamous cell carcinoma growth via beta-adrenoceptors in vitro and in vivo.
复制标题
4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮在体外和体内通过 β-肾上腺素受体促进食管鳞状细胞癌的生长。
DOI：
10.1371/journal.pone.0118845
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Li P
中科院分区：
文献类型：
--
作者：
Zhang N;Sun X;Sun M;Zhu S;Wang L;Ma D;Wang Y;Zhang S;Li P
吸烟是食管鳞状细胞癌（ESCC）的危险因素。它含有几种已知的致癌物质，可以引发和促进肿瘤发生以及转移。亚硝胺4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）是烟草中最强的致癌物之一，我们前期的研究表明其在食管鳞癌的发展中具有促增殖作用。最近，NNK被鉴定为β 1和β 2肾上腺素受体的激动剂。因此，我们假设NNK的促癌作用可能是通过ESCC中的β-肾上腺素受体介导的。因此，我们在体外和体内研究了NNK在ESCC中的综合作用，发现NNK促进许多致癌特征，包括ESCC细胞增殖和异种移植肿瘤生长以及ESCC细胞迁移和侵袭。Western blotting显示NNK诱导磷酸化ERK 1/2、cyclin D1、Bcl-2和血管内皮生长因子表达上调，Bax表达下调。重要的是，NNK在ESCC中的致癌作用和改变的蛋白质表达在一定程度上通过下调β 1和β 2肾上腺素受体而逆转，其中β 2肾上腺素受体表现出更大的拯救作用。总之，我们的体外和体内结果表明，NNK通过β-肾上腺素受体在ESCC中发挥致癌作用。β_2-肾上腺素能受体在此过程中可能起更重要的作用。我们的研究结果可能为吸烟相关食管鳞癌的化学预防和治疗提供了一种策略。
Cigarette smoke is a risk factor for esophageal squamous cell carcinoma (ESCC). It contains several carcinogens known to initiate and promote tumorigenesis as well as metastasis. The nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the strongest carcinogens in tobacco and our previous studies have shown its proliferation-promoting role in the progression of ESCC. Recently, NNK was identified as an agonist for both beta1- and beta2-adrenoceptors. Thus, we hypothesized that the cancer-promoting effect of NNK was likely mediated through beta-adrenoceptors in ESCC. Therefore, we investigated the comprehensive role of NNK in ESCC in vitro and in vivo, and found that NNK promoted many oncogenic features including ESCC cell proliferation and xenograft tumor growth as well as ESCC cell migration and invasion. Western blotting showed that NNK induced significant up-regulation of phosphorylated ERK1/2, cyclin D1, Bcl-2, and vascular endothelial growth factor as well as down-regulation of Bax. Importantly, the oncogenic effects of NNK in ESCC and the altered protein expression were reversed to some extent by down-regulation of beta1- and beta2-adrenoceptors with the beta2-adrenoceptor showing a greater rescue effect. Taken together, our in vitro and in vivo results demonstrate that NNK plays an oncogenic role in ESCC through beta-adrenoceptors. Furthermore, beta2-adrenoceptor might play a more important role in this process. Our findings might provide a chemoprevention and therapy strategy for cigarette smoke-related ESCC carcinogenesis.
登录
查看更多内容
DOI：
10.1016/j.lungcan.2013.09.012
发表时间：
2013-12
期刊：
Lung cancer (Amsterdam, Netherlands)
影响因子：
--
作者：
Aizawa K;Liu C;Veeramachaneni S;Hu KQ;Smith DE;Wang XD
通讯作者：
Wang XD
影响因子：
9.3
作者：
Lambert, R.;Hainaut, P.
通讯作者：
Hainaut, P.
影响因子：
4.7
作者：
Lin Y;Totsuka Y;He Y;Kikuchi S;Qiao Y;Ueda J;Wei W;Inoue M;Tanaka H
通讯作者：
Tanaka H
影响因子：
4.6
作者：
Duell, Eric J.
通讯作者：
Duell, Eric J.
DOI：
10.1158/1541-7786.mcr-11-0332
发表时间：
2012-02
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Al-Wadei MH;Al-Wadei HA;Schuller HM
通讯作者：
Schuller HM