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Toll 样受体 9 激动剂通过激活 NF-κB 上调前列腺癌细胞中环氧化酶-2 的表达。

Toll-like receptor 9 agonists up-regulates the expression of cyclooxygenase-2 via activation of NF-kappaB in prostate cancer cells.

机构信息

Department of Urology, Third Affiliated Hospital of Sun Yat-Sen University, 600# Tianhe Road, 510630, Guangzhou, People's Republic of China.

出版信息

Mol Biol Rep. 2010 Apr;37(4):1849-55. doi: 10.1007/s11033-009-9620-5. Epub 2009 Jul 19.

DOI:10.1007/s11033-009-9620-5
PMID:19618291
Abstract

CpG-oligonucleotides (CpG-ODNs), mimicking bacterial DNA, have recently been shown to stimulate prostate cancer invasion in vitro via Toll-like receptor 9 (TLR9). Since cyclooxygenase 2 (COX-2), frequently overexpressed in multiple tumor types including prostate cancer, is a causal factor for tumor development, invasion and metastasis, an interesting question is raised whether TLR9 regulates COX-2 expression in prostate cancer cells. To address this question, herein we examined COX-2 expression in PC-3 cells stimulated with different doses and time courses of CpG-ODNs. The regulatory role of NF-kappaB in TLR9-mediated COX-2 expression was also investigated. CpG-ODN was found to up-regulate the expression of COX-2 in PC-3 cells in a dose- and time-dependent manner, but have little impact on COX-1 expression. Moreover, CpG-ODN also promoted nuclear translocation and activation of NF-kappaB, which appeared to be required for COX-2 induction by CpG-ODN. Overall, TLR9 up-regulates COX-2 expression in prostate cancer cells, at least partially through the activation of NF-kappaB, which may be implicated in tumor invasion and metastasis.

摘要

CpG-寡核苷酸(CpG-ODNs),模拟细菌 DNA,最近被证明可以通过 Toll 样受体 9(TLR9)刺激前列腺癌细胞体外侵袭。由于环氧化酶 2(COX-2)在包括前列腺癌在内的多种肿瘤类型中过度表达,是肿瘤发生、侵袭和转移的一个因果因素,因此提出了一个有趣的问题,即 TLR9 是否调节前列腺癌细胞中的 COX-2 表达。为了解决这个问题,本文研究了不同剂量和时间进程的 CpG-ODN 刺激 PC-3 细胞后 COX-2 的表达。还研究了 NF-kappaB 在 TLR9 介导的 COX-2 表达中的调节作用。结果发现,CpG-ODN 以剂量和时间依赖的方式上调 PC-3 细胞中 COX-2 的表达,但对 COX-1 表达影响不大。此外,CpG-ODN 还促进了 NF-kappaB 的核易位和激活,这似乎是 CpG-ODN 诱导 COX-2 所必需的。总的来说,TLR9 上调前列腺癌细胞中 COX-2 的表达,至少部分是通过 NF-kappaB 的激活,这可能与肿瘤的侵袭和转移有关。

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