Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-α-treated A549 cells

被引：37

作者：

Sun, Lixin ^{[1
]}

Zhang, Shuang ^{[1
]}

Jiang, Zhenzhou ^{[1
]}

Huang, Xin ^{[1
]}

Wang, Tao ^{[1
]}

Huang, Xiao ^{[1
]}

Li, Han ^{[1
]}

Zhang, Luyong ^{[1
]}

机构：

[1] China Pharmaceut Univ, Jiangsu Ctr Drug Screening, Nanjing 210009, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2011年 / 416卷 / 1-2期

关键词：

Triptolide; COX-2; mRNA stability; HuR; NF-KAPPA-B; CARCINOMA-CELLS; LUNG-CANCER; CYCLOOXYGENASE-2; PATHWAYS; ELEMENT; HUR; INVOLVEMENT;

D O I：

10.1016/j.bbrc.2011.11.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Cyclooxygenase-2 (COX-2) over-expression is frequently associated with human non-small-cell lung cancer (NSCLC) and involved in tumor proliferation, invasion, angiogenesis and resistance to apoptosis. In the present study, the effects of triptolide on COX-2 expression in A549 cells were investigated and triptolide was found to inhibit TNF-alpha-induced COX-2 expression. In our further studies, it was found that triptolide decreased the half-life of COX-2 mRNA dramatically and that it inhibited 3'-untranslated region (3'-UTR) fluorescence reporter gene activity. Meanwhile, triptolide inhibited the HuR shuttling from nucleus to cytoplasm. After triptolide treatment, decreased COX-2 mRNA in pull-down experiments with anti-HuR antibodies was observed, indicating that the decreased cytoplasmic HuR is responsible for the decreased COX-2 mRNA. Taken together, our results provided evidence for the first time that triptolide inhibited COX-2 expression by COX-2 mRNA stability modulation and post-transcriptional regulation. These results provide a novel mechanism of action for triptolide which may be important in the treatment of lung cancer. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：99 / 105

页数：7

共 22 条

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Targeting COX-2 expression by natural compounds: A promising alternative strategy to synthetic COX-2 inhibitors for cancer chemoprevention and therapy [J].