Influence of caloric restriction on constitutive expression of NF-κB in an experimental mouse astrocytoma.
Influence of caloric restriction on constitutive expression of NF-κB in an experimental mouse astrocytoma.
复制标题
DOI：
10.1371/journal.pone.0018085
复制
发表时间：
2011-03-30
期刊：
影响因子：
3.7
通讯作者：
Mukherjee P
中科院分区：
文献类型：
--
作者：
Mulrooney TJ;Marsh J;Urits I;Seyfried TN;Mukherjee P
目前用于治疗原发性恶性脑癌的许多标准疗法在很大程度上被视为姑息性的，最终是因为这些常规策略在许多情况下已被证明会降低患者的生活质量，同时仅适度增加生存期。我们建议，热量限制（CR）是脑癌管理的替代代谢疗法，不仅可以提高生存率，还可以降低与疾病相关的发病率。尽管我们已经证明CR通过多种分子和生化机制控制肿瘤生长并提高生存率，但关于CR在调节脑肿瘤组织炎症中所起的作用的信息很少。核因子κB（NF-κB）的磷酸化和激活导致许多基因的反式激活，包括编码环氧合酶-2（考克斯-2）和同种异体移植炎性因子-1（AIF-1）的那些基因，这两种蛋白质主要由炎性和恶性癌细胞表达。在体外和体内研究中，考克斯-2已显示出增强炎症和促进肿瘤细胞存活。在目前的报告中，我们证明了NF-κB的p65亚基在CT-2A肿瘤中的表达与对侧正常脑组织相比是组成性的，我们还表明CR降低了（i）肿瘤组织中NF-κ B依赖性基因考克斯-2和AIF-1的磷酸化和转录激活程度，以及（ii）CT-2A恶性小鼠星形细胞瘤中NF-κB下游的促炎标记物[例如巨噬细胞炎性蛋白-2（MIP-2）]的表达。总的来说，我们的数据表明NF-κB炎症通路在CT-2A星形细胞瘤中被组成性激活，CR靶向该通路和炎症。CR可以有效地减少恶性脑肿瘤的生长，部分是通过抑制原发性脑肿瘤中的炎症。
Many of the current standard therapies employed for the management of primary malignant brain cancers are largely viewed as palliative, ultimately because these conventional strategies have been shown, in many instances, to decrease patient quality of life while only offering a modest increase in the length of survival. We propose that caloric restriction (CR) is an alternative metabolic therapy for brain cancer management that will not only improve survival but also reduce the morbidity associated with disease. Although we have shown that CR manages tumor growth and improves survival through multiple molecular and biochemical mechanisms, little information is known about the role that CR plays in modulating inflammation in brain tumor tissue. Phosphorylation and activation of nuclear factor κB (NF-κB) results in the transactivation of many genes including those encoding cycloxygenase-2 (COX-2) and allograft inflammatory factor-1 (AIF-1), both of which are proteins that are primarily expressed by inflammatory and malignant cancer cells. COX-2 has been shown to enhance inflammation and promote tumor cell survival in both in vitro and in vivo studies. In the current report, we demonstrate that the p65 subunit of NF-κB was expressed constitutively in the CT-2A tumor compared with contra-lateral normal brain tissue, and we also show that CR reduces (i) the phosphorylation and degree of transcriptional activation of the NF-κB-dependent genes COX-2 and AIF-1 in tumor tissue, as well as (ii) the expression of proinflammatory markers lying downstream of NF-κB in the CT-2A malignant mouse astrocytoma, [e.g. macrophage inflammatory protein-2 (MIP-2)]. On the whole, our date indicate that the NF-κB inflammatory pathway is constitutively activated in the CT-2A astrocytoma and that CR targets this pathway and inflammation. CR could be effective in reducing malignant brain tumor growth in part by inhibiting inflammation in the primary brain tumor.
登录
查看更多内容
DOI：
10.1165/ajrcmb.19.3.3114
发表时间：
1998-09-01
影响因子：
6.4
作者：
Dong, WM;Selgrade, MK;Kari, FW
通讯作者：
Kari, FW
影响因子：
4.8
作者：
Clément, K;Viguerie, N;Langin, D
通讯作者：
Langin, D
影响因子：
11.5
作者：
Carlson, Marc R. J.;Pope, Whitney B.;Cloughesy, Timothy F.
通讯作者：
Cloughesy, Timothy F.
影响因子：
4.7
作者：
FLAVIN, HJ;WIERASZKO, A;SEYFRIED, TN
通讯作者：
SEYFRIED, TN
影响因子：
5.5
作者：
Armstrong, DA;Major, JA;Hamilton, TA
通讯作者：
Hamilton, TA