Study the mechanisms of the antiangiogenesis activity of magnolol in colon cancer cells : role of PEDF and ERK5

• Main Authors: Yi-Wen Cheng, 鄭伊雯
• Other Authors: Tz-Chong Chou
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/50848638047784082753

碩士 === 國防醫學院 === 生理學研究所 === 101 === Colon cancer is the most common malignancy and the highly leading cause of cancer-related mortality in the world. Angiogenesis plays an important role in tumor progression. Activation of hypoxia-inducible factors-1 alpha (HIF-1α) during hypoxia, triggers vascular endothelial growth factor (VEGF), an important factor causing tumor angiogenesis and progression. It’s well known that MAPK signaling enhanced HIF-1α activation. The extracellular signal-regulated kinase-5 (ERK5), one of the MAPK family, has been reported to stimulate tumor angiogenesis and metastasis. The pigment epithelial-derived factor (PEDF) is a potent endogenous inhibitor of angiogenesis and has been proposed to be a tumor suppressor in a variety of tumors. Magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, has been reported to have a variety of pharmacological activities However, in hypoxia condition, effects of magnolol on PEDF-mediated signaling pathway and suppress HIF-1α/VEGF-induced angiogenesis in HCT116 colon cancer cells are still unreported. Our data showed that treatment with magnolol dose-dependently inhibited hypoxia-induced ROS formation, p-ERK5, HIF-1α, VEGF expression accompanied by an attenuation of hypoxia-induced cell migration and invasion. In addition, magnolol up-regulated PEDF under hypoxia condition. In conclusion, we demonstrate that magnolol may be a potential anti-angiogenesis drug in HCT116 human colon cancer by elevating PEDF expression and in turn diminishing ROS/ HIF-1α/ VEGF pathway.