日本分子生物学会/日本生化学会

16:45 〜 18:45

[2LBA034] Caffeine Suppresses the Progression of Human Glioblastoma via Cathepsin B and MAPK Signaling Pathway

〇Yu-chen Cheng1、You-Ming Ding2、Ying Chen1,2 (1.Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan、2.Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan)

Caffeine, Glioma, Cathepsin B, MAPK, Invasion

Glioblastoma has aggressive proliferative and invasive properties. We investigated the effect of caffeine on the invasion and the anti-cancer effect in human glioblastomas. Caffeine reduced the invasion in U-87MG, GBM8401 and LN229 cells. Caffeine decreased mRNA, protein expression, and activity of cathepsin B. Besides, mRNA and protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) was upregulated by caffeine treatment, whereas matrix metalloproteinase-2 (MMP-2) was downregulated. The expression of Ki67, p-p38, phospforylated extracellular regulated protein kinases (p-ERK), and membranous integrin β1 and β3 was decreased by caffeine. The Rho-associated protein kinase (ROCK) inhibitor, Y27632, blocked the caffeine-mediated reduction of cathepsin B, phosphorylated focal adhesion kinase (p-FAK), and p-ERK, and invasion. Moreover, caffeine decreased the tumor size, cathepsin B and Ki67 expression in animal model. Caffeine reduced the invasion of glioma cells through ROCK-cathepsin B/FAK/ERK signaling pathway and tumor growth in orthotopic xenograft animal model, supporting the anti-cancer potential in glioma therapy.