| Summary: | 碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 96 === According to the 2006 census of department of health, Executive Yuan, ROC, oral cancer ranks fourth in the mortality rate of male cancer patient in Taiwan. Areca chewing has been affirmed as the major risk factor of oral caner. Arecoline is the major ingredient of areca nut and the concentration can reach 0.9 mM in saliva. Recent studies show that Cyr61 is expressed at high level in oral cancer.
Cyr61-expressed clones could promote in vivo tumor formation and angiogenesis in SCID mice. We identify 0.6mM arecoline can induce the expression of Cyr61 in oral epithelial cell SG, Ca9-22 and KB lines. Arecoline also can induce generation of ROS . ROS inhibitor, N-acetylcysteine can inhibite the expression of Cyr61 in KB cell. Arecoline can activate ras-related small GTPase Rac1. Rac1 inhibitor, NSC23766 and p38 MAPK inhibitor, SB203580 and MSK1 inhibitor, H89 also inhibited the expression of Cyr61 induced by arecoline whereas NSC23766 and SB203580 did not inhibit the generation of ROS. Western blotting showed that arecoline activated CREB. Arecoline also induced the expression of Egr-1.
Furthermore, curcumin, an AP-1inhibitor, inhibited the arecoline-induced Cyr61 expression. Thus, arecoline may induce the expression of Cyr61 through ROS-Rac1-p38 MAPK-MSK-CREB signaling pathway. HDAC inhibitor, SAHA or TSA increased the induction of Cyr61 by arecoline. Histone acetylation may play an important role in the expression of Cyr61 induced by arecoline. Blocking the arecoline-induced Cyr61 signaling may provide an alternative therapeutic approach for the treatment of oral cancer in Taiwan.
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