| Summary: | 碩士 === 國防醫學院 === 生物及解剖學研究所 === 102 === Glioma is the most malignant tumor in central nervous system with highly invasive and aggressive abilities. Surgery is not easy to clean the tumor completely and the prognosis is poor. The purpose of this study is to investigate the mechanisms of caffeine in the regulation of invasion in human glioma cells. The first part of this study showed that caffeine reduced the invasion in U87MG, GBM8401, and LN229 glioma cells. U87MG glioma cells were used throughout this study. Caffeine reduced the activity of matrix metalloproteinase-2 (MMP-2) and cathepsin B. Besides, caffeine suppressed mRNA and protein expressions of MMP-9 and cathepsin B. Moreover caffeine downregulated the expressions of integrin β3, phosphorylated focal adhesion kinase (p-FAK), phosphorylated extracellular-signal-regulated kinase (p-ERK), and phosphorylated p38. Besides, caffeine decreased membrane expressions of integrin β1 and β3. The inhibitor of Rho-associated protein kinase (ROCK), Y27632, prevented the caffeine-reduced p-FAK, p-ERK, and invasion,suggesting that caffeine decreased theexpression of integrin β3, p-FAK, p-ERK and invasion by ROCK. On the other hand, caffeine decreased the binding of intergrin β3 and urokinase-type plasminogen activator receptor (uPAR), which may also contribute to the caffeine-suppressed p-FAK and p-ERK. In addition, caffeine suppressed the expression of p-p38 which may lead to the decrease of MMP-9 and cathepsin B, the increase of tissue inhibitors of metalloproteinases-1 (TIMP-1), and contribute to the inhibition of invasion.
The second part of this study is to investigate the effect of caffeine on glioma xenograft growth 25 mg/kg and 50 mg/kg intraperitoneal injection of caffeine treatment groups were compared with PBS control group starting from day 6 to day 14 after cell injection to the brain. Histopathological examination of brain using hematoxylin and eosin staining showed that caffeine reduced glioma tumor size in vivo. Caffeine displayed no significant toxicity effect on the alteration of body weight. In conclusion, caffeine suppressed the invasion of human glioma cells through the inhibition of ROCK- p-FAK/integrin β3/p-ERK and reduced glioma tumor size.
|
|---|
