Ling Zhi-8 inhibits EGFR signaling pathways-mediated EMT in lung cancer cells

• Main Authors: Tung-Yi Lin, 林東毅
• Other Authors: Hsien-Yeh Hsu
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/59224975227450337450

碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系 === 100 === Ling Zhi-8 (LZ-8) is a human immune-modulatory protein from Ganoderma lucidum. Our recent study demonstrated that LZ-8 effectively can prevent lung cancer cell proliferation; however, the mechanism of recombinant LZ-8 (rLZ-8) exhibits anti-metastasis property is unclear. Epithelial-mesenchymal transition (EMT) process has been regarded as the critical event in tumor metastasis and induced by multi-signaling pathway. The epidermal growth factor receptor (EGFR)-mediated signal transductions play an important role in tumor progression and EMT process. Regulation of Snail, through EGF-induced downstream signaling activation, plays a pivotal role of EMT determinate. We hypothesized that rLZ-8 may suppress the EGFR-driven EMT in human non small cell lung cancer cells (NSCLC). Treatment of lung cancer cells with rLZ-8 induced E-cadherin and inhibited N-cadherin as well as it significantly inhibits EGFR-induced cell motility in vitro. The mechanism of rLZ-8 mediated inhibition of EMT was corroborated by suppressing autophosphorylation of FAK and reduces Src activity. Concomitantly, rLZ-8 also suppresses ERK and AKT downstream pathways and Snail expression. It was further demonstrated that rLZ-8 suppresses tumor growth and metastasis in Lewis lung carcinoma cells-bearing mice. Interesting, rLZ-8 significantly and specifically downregulates EGFR protein level in vitro and in vivo. In conclusion, the role of rLZ-8 in the regulation of EMT was inhibited by downregulation of EGFR level and by suppression of FAK activity. These findings suggest that rLZ-8 may be a potentially anti-metastasis agent in the treatment of human NSCLC.