GMI-induced autophagy: Investigation of FAK/Src signaling pathway in human non-small cell lung cancer

• Main Authors: Yi-Ling Hsieh, 謝宜玲
• Other Authors: Hsien-Yeh Hsu
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/efzxrt

碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系 === 103 === GMI, an immune-modulatory protein from Ganoderma microsporum, exhibits immunomodulatory and antitumor activity. Lung cancer is the leading cause of cancer incidence and death in the world. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is ubiquitously overexpressed and activated in several solid cancers. It regulates various signaling pathways to promote cancer cells growth and metastasis. Autophagy is an important homeostatic cellular recycling mechanism that involves cells degradation of malfunctioning proteins or damaged organelles. Here we demonstrated that GMI induced autophagy in non-small cell lung cancer (NSCLC), and down-regulated phosphorylation of FAK and Src. Specifically, we found that inhibition of autophagy by inhibitor treatment (chloroquine) or shRNA knockdown system rescued the phosphorylation level of Src and enhanced cell death in cancer cells upon GMI treatment. These results suggest that GMI induces autophagic flux in NSCLC. Autophagic flux generally may be considered as cyto-protective effect. Thus, Combination of autophagy inhibitor with GMI may a strategy to increase GMI anti-cancer efficacy.