Effects of angiotensin II blockade, PPARγ agonist and antioxidant on Arecoline-induced effects in LLC-PK1 cells
| Autor: | Jun-Qing Wang, 王俊清 |
|---|---|
| Rok vydání: | 2005 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 93 Betel quid increases the risk of oral cancer by damaging oral mucosal epithelial cells. Arecoline is the most important components of betel quid which damages oral mucosa epithelial cells. Thus, we studied the effects caused by arecoline in LLC-PK1,including the inhibition of cell growth and cell cycle, and the increase of extracellular matrices. We also studied the molecular mechanisms of arecoline-induced effects, including ERK (extracellular activated kinase)、PI3 kinase、PKC (protein kinase C) and JAK (Janus kinase)-STAT (signal transducers and activators of transcription) pathway. Renoprotective drugs, such as: Captopril(angiotensin converting enzyme inhibitor)、Losartan (angiotensin II type I receptor antagonist)、Rosiglitazone (PPARγ agonist)and N-acetylcysteine (antioxidant) were also studied in terms of the effects on arecoline-induced effects. Results: Arecoline (250 µM) inhibited cell growth and arrested cells at G0/G1. Arecoline also decreased cyclin D1, cyclin D2 while increasing P21 and 3TP-Lux promoter (TGF-β bioactivity), phTG5(TGF-β) promoter and p21PF promoter activities. PD98059 (ERK inhibitor) reversed arecoline-induced decrease in cyclin D1 and cyclin D2. Stausporin C ( PKC inhibitor) reverses arecoline-induced decrease in cyclin D1 and cyclin D2. Among the four renoprotective drugs (captopril, losartan, rosiglitazone and N-acetylcysteine), Captopril and N-acetylcysteine reversed arecoline-induced decrease in cyclin D1. Captopril, losartan and N-acetylcysteine reversed arecoline-induced decrease in cyclin D2. Captopril and N-acetylcysteine reversed arecoline-induced cell growth inhibition and cell cycle inhibition. Captopril and N-acetylcysteine also reversed Arecoline-induced increase in 3TP-Lux、phTG5、p21PF promoter activities in LLC-PK1 cells. Conclusion：Arecoline inhibited LLC-PK1 cell growth by way of the TGF-β, MAP kinase and PKC pathways while Captopril and N-acetylcysteine reversed Arecoline-induced effects in LLC-PK1 cells. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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