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

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-α-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.

► Triptolide inhibited COX-2 expression and the half-life of COX-2 mRNA is decreased.
► The HuR protein shuttling from nucleus to cytoplasm is inhibited by triptolide.
► Triptolide inhibited 3′-UTR fluorescence reporter gene activity.
► COX-2 mRNA binding to HuR is decreased by triptolide in pull-down experiments.