위암세포 AGS세포에서 Triptolide에 의한 urokinase plasminogen activator receptor 발현조절 = Triptolide blocks tumor promoter-induced uPAR expression via suppression of ROS and NF-kB signals in human gastric AGS cells

다국어 초록 (Multilingual Abstract)

Overexpression of uPAR has been known to correlate closely with tumor cell invasion and strategies to down-regulate their expression may ultimately be of clinical utility. In this study, we investigated the effects of triptolide, a diterpenoid triepoxide extracted Chinese herb Tripterygium wilfordii Hook f., on the uPAR induction in human gastric cancer AGS cells. Triptolide inhibited the phorbol 12-myristate 13-acetate (PMA) - induced uPAR mRNA and protein expression in a dose-dependent manner. Triptolide treatment was found to reduce the uPAR transcriptional activity. The stability of uPAR transcripts was not altered by triptolide treatment. To study the mechanisms for the triptolide-mediated regulation of uPAR, the signals involved in uPAR induction by PMA were investigated. The inhibitors of extracellular signal-regulated kinases 1 and 2 (Erk-1/2, PD98059), c-Jun N-terminal kinases (JNK, SP600125) and NF-kB (BAY11-7082) are inhibited the PMA-induced uPAR expression suggesting that PMA induced uPAR via multiple signals. Triptolide suppressed the PMA-induced the NF-κB activation but not the activation of Erk-1/2 and JNK. The suppression of NF-kB activation by triptolide was confirmed by NF-kB-dependent luciferase, dominant negative NF-kB mutants and I-kB degradation studies. Triptolide also abrogated the PMA-induced production of ROS, which are known to upstream modulator for NF-kB activation. These results suggest that triptolide may exert at least part of its anti-invasive effect in gastric cancer by controlling uPAR expression through the suppression of NF-kB activation and the production of ROS.

목차 (Table of Contents)

• Abstract (in English) 1
• Introduction 3
• Materials and Methods 6
• Results 12
• Discussion 29
• References 32
• Abstract ( in Korean ) 38