Effects of extract of Reishi polysaccharides on TGF-β1-mediated epithelial-to-mesenchymal transition in human non-small-cell lung cancer A549 cells

• Main Authors: Mei-Hsiu Lin, 林美秀
• Other Authors: Hsien-Yeh Hsu
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/40821991421077433274

碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系暨研究所 === 98 === Lung cancer is the leading cause of cancer death. And the five-year relative survival rate is only about 15%. There are many treatments for lung cancer patients. It depends on the diagnosed stage. Nowadays the treatment has restricted. The most important reason is metastasized when diagnosed. Epithelial-mesenchymal transition (EMT) has been regarded as the critical event in tumorigenesis and is typically induced by a multifunctional cytokine, transforming growth factor (TGF)-β1. Ganoderma lucidum (Ling-zhi or Reishi) has been used for a long time in tradition herbal medicine. It contains many bioactive components. Polysaccharide is one of the bioactive compounds. We used the extract of Reishi polysaccharides (EORP) in our research. To investigate the effects of EORP on TGF-β1-mediated EMT in lung cancer A549 cells. EORP reverses TGF-β1-induced EMT morphological changes in A549 cells, in addition, the epithelial markers are up-regulated; alternatively, mesenchymal markers are down-regulated. To further analyze the mechanism for altering EMT, we found that phosphorylation of Smad2/3 proteins is reduced when cells treated with EORP for 3 h, meanwhile, EORP inhibits TGF-β1-induced translocation of Smad2/3-protein from the cytoplasm to the nucleus. On the other hand, EORP treatment of cells for 3 h, it decreases Smad4 protein expression followed by reducing Smad4 translocation to nucleus. Furthermore, the transcription factor snail protein is inhibited after treated with EORP for 3 h. In addition, EORP decreases the levels of TGFβ1 and TGFβ receptor II. We also found that cells treated with EORP results in the inhibition of TGF-β1-induced cell migration and invasion. Our results show that EORP inhibits the TGF-β1-mediated epithelial-mesenchymal transition via inhibition of the Smad and snail protein expression in NSCLC A549 cells.