Signal transduction pathways of arecoline-induced AKR1B10 expression in oral epithelial cells

• Main Authors: Sheng-Jiun Shie, 謝昇峻
• Other Authors: Yen-Ping Kuo
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/3m46z5

碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 107 === In Taiwan, oral cancer is the sixth leading cause of death from cancer in both genders and ranks the fourth in males in 2011. Although treatment of early stage oral cancer (stage I or II) is frequently successful, disease relapses still occur in about 30% patient. For patients with advanced disease, fewer than 30% of them can be cured. Despite recent advances in surgery, radiotherapy and chemotherapy, the overall 5-year survival rate for patients with oral cancer has not changed during the past two decades. Thererfore, continued investigation of new diagnostic markers and chemotherapeutic agents is needed. We found Aldo-keto reductase 1B10 (AKR1B10) is induced by an areca nut alkaloid, arecoline. Arecoline induce AKR1B10 synthesis in a dose- and time- depend Manner in SAS and Ca9-22 cell. We aimed to examine the possible signal transduction pathways involved in TGF-β1-induced AKR1B10 expression in SAS and Ca9-22 cell, we found the effect that Arecoline induces AKR1B10 activation was inhibited by TGF-β1 neutralizing antibody, ALK5 inhibitor (SB431542) and Smad3 inhibitor (SIS3).We have also shown that PI3K inhibitor (LY294002), ERK inhibitor (PD98059), JNK inhibitor (SP600125), and Src inhibitor (PP2) are involved in the TGF-β1-induced AKR1B10 in SAS cell.Furthermore, Cucurmin completely inhibited Arecoline-induced AKR1B10 synthesis and inhibition is dose-dependent. We investigate whether AKR1B10 play a role in regulating chemoresistant in SAS cells. We found inhibited AKR1B10 significantly inhibited chemoresistant in HSC3 cell. KEYWORDS: Arecoline、oral cancer、Aldo-keto reductase 1B10，AKR1B10、Reactive oxygen species (ROS)、Curcumin、Transforming growth factor-β1