The inhibitory effects of extract of Reishi polysaccharides on proliferation of human non-small-cell lung cancer A549 cells
| Autor: | Han-Ning Wei, 魏涵寧 |
|---|---|
| Rok vydání: | 2010 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 98 An extract of Reishi (Ganoderma lucidum or Ling-Zhi) polysaccharides (EORP), a natural bioactive glycan isolated from a water-soluble fraction of Reishi, has been shown to exhibit immuno-modulating and anti-tumor activities. However, the molecular mechanisms responsible for the inhibitory effects of EORP on the proliferation of lung cancer cells remain less understood. It has been reported that endothelin receptor type A (ETAR) activation by endothelin-1 (ET-1) triggers the activation of a network of a multiple signaling including PI3K/AKT and MAPK pathways to contribute to tumor growth. Further more, ET-1 has been detected and ETAR is overexpressed in pulmonary adenocarcinomas. Both show that ET axis plays an important role in tumor proliferation. In this study, we demonstrate that EORP inhibits A549 cells growth via induction of cell cycle arrest at G0/G1 phase. Moreover, EORP down-regulates the expression of ETAR and blocking activation of downstream phosphoinositide 3-kinase (PI3K), Akt and extracellular signal-regulated kinases (ERK). In addition, the regulation of EORP in ETAR causes an inhibition of the transactivation and cross-talk between ETAR and epidermal growth factor receptor (EGFR) by decreasing activation of Src. The inhibition of ETAR and EGFR pathways resulted in reducing the phosphorylation of GSK3β, and leading to down-regulate the translocation of β-catenin to nuclear to repress the expression of cyclin D1, finally suppressing proliferation of A549 cell. Since that cross-talk between different receptors has been implicated in many cancers, the inhibitory effects of EORP indicate a new therapeutic opportunities for cancer. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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