| ABSTRACT | 第4-7页 |
| 摘要 | 第8-14页 |
| INTRODUCTION | 第14-32页 |
| 1.1 Gastric cancer and colorectal cancer are two of the most dangerous tumors | 第14-16页 |
| 1.1.1 Gastric Cancer | 第14-15页 |
| 1.1.2 Coleclteral Cancer | 第15-16页 |
| 1.2 Cell death | 第16-21页 |
| 1.2.1 Apoptosis | 第16-17页 |
| 1.2.2 The Extrinsic Pathway | 第17-18页 |
| 1.2.3 NF-κB signal associated with the Extrinsic Pathway | 第18-19页 |
| 1.2.4 The Intrinsic Pathway | 第19-20页 |
| 1.2.5 The Final Pathway: Caspases | 第20-21页 |
| 1.3 Reactive Oxygen Species (ROS) | 第21-22页 |
| 1.4 PI3K/Akt pathway and cell apoptosis | 第22-24页 |
| 1.5 p53 signal and cell arrest | 第24-26页 |
| 1.5.1 p53 associated with DNA damage | 第24-25页 |
| 1.5.2 Cell cycle arrest at S phase and DNA damage | 第25-26页 |
| 1.6 JAK-STAT signal in apoptosis | 第26-28页 |
| 1.7 The anti-cancer natural products of mushroom extracts | 第28-30页 |
| 1.7.1 Cordycepin | 第29页 |
| 1.7.2 Illudin S | 第29-30页 |
| 1.7.3 Lentinan | 第30页 |
| 1.8 The object of the thesis | 第30-32页 |
| MATERIALS AND METHODS | 第32-38页 |
| 2.1 Chemical and Regents | 第32页 |
| 2.2 Ethics/guidelines | 第32页 |
| 2.3 Cell Culture | 第32-33页 |
| 2.4 Determination of cell cytotoxicity by MTT | 第33页 |
| 2.5 Cell morphological Change | 第33-34页 |
| 2.5.1 DAPI staining | 第33页 |
| 2.5.2 Hoechst staining | 第33-34页 |
| 2.5.3 Acridine Orange staining | 第34页 |
| 2.6 Annexin V/PI assays for apoptosis | 第34页 |
| 2.7 Cell cycle analysis | 第34-35页 |
| 2.8 Determination of mitochondrial trans-membrane potential (MMP) | 第35页 |
| 2.9 Determination of Intracellular Reactive Oxygen Species (ROS) | 第35页 |
| 2.10 Western-blot analysis | 第35-36页 |
| 2.11 Transient Transfection and Luciferase Report | 第36页 |
| 2.12 Real-time q PCR analysis | 第36-37页 |
| 2.13 Statistical analysi S | 第37页 |
| 2.14 Docking system test | 第37-38页 |
| RESULTS | 第38-68页 |
| Part Ⅰ: Cordycepin induces apoptosis in SGC-7901 cells through mitochondrial extrinsic phosphorylation of PI3K/Akt with generating ROS | 第40-50页 |
| 3.1.1 Cordycepin induces SGC-7901 cells cytotoxicity | 第40-41页 |
| 3.1.2 Cordycepin induces SGC-7901 cells morphological change | 第41页 |
| 3.1.3 Cordycepin induces SGC-7901 cells apoptosis | 第41-42页 |
| 3.1.4 Cordycepin induces SGC-7901 cells apoptosis through mitochondrial extrinsic pathways | 第42-43页 |
| 3.1.5 Cordycepin induces SGC-7901 cells mitochondrial membrane collapse | 第43-44页 |
| 3.1.6 Cordycepin induces apoptosis in SGC-7901 cells by generating reactive oxygen species | 第44-45页 |
| 3.1.7 Cordycepin induces SGC-7901 cells apoptosis through JAK2/STAT3 and PIA3K/AKT pathways | 第45-46页 |
| 3.1.8 Cordycepin induces SGC-7901 cells cycle arrest at S phase | 第46-50页 |
| Part Ⅱ Illudin S Regulates PI3K/AKT and JAK2/STAT3 Signaling in Gastric (SGC-7901) and Colorectal (SW480) Cancer Cell Lines | 第50-64页 |
| 3.2.1 Illudin S induces SGC-7901 and SW480 cells cytotoxicity | 第50-51页 |
| 3.2.2 Cordycepin induces SGC-7901 and SW480 cells morphology changes | 第51页 |
| 3.2.3 Illudin S induces SGC-7901 and SW480 cells apoptosis | 第51-52页 |
| 3.2.4 Cordycepin induces SGC-7901 and SW480 cells apoptosis through mitochondrial extrinsic and intrinsic pathway | 第52-54页 |
| 3.2.5 Illudin S induces SGC-7901 and SW480 cells apoptosis through mitochondrial membrane collapse | 第54-55页 |
| 3.2.6 Illudin S induces SGC-7901 and SW480 cells apoptosis through the generation of ROS | 第55-56页 |
| 3.2.7 Illudin S induces SGC-7901 and SW480 cells apoptosis through regulating JAK2/STAT3 pathways | 第56-59页 |
| 3.2.8 Illudin S induces SGC-7901 and SW480 cells apoptosis through regulating PI3K/Akt pathways | 第59-61页 |
| 3.2.9 Illudin S inhibited SGC-7901 and SW480 cells by stopping cell cycle arrest at S phase | 第61-64页 |
| PART Ⅲ : Auto-Docking of Cordycepin and Illudin S to Fas and DR3 (TNFɑR) | 第64-68页 |
| DISCUSSION | 第68-74页 |
| 4.1 The mushroom extracts have great prospect in development of anti- tumor drug | 第68-69页 |
| 4.2 Cordycepin and Illudin S induce cells apoptosis trough mitochondrial extrinsic and intrinsic pathway | 第69-70页 |
| 4.3 Cordycepin and Illudin S induces cell cycle at S-phase by generate ROS and activating p53 signaling pathways | 第70-71页 |
| 4.4 Cordycepin and Illudin S induce apoptosis by regulating JAK2 / STAT and PI3K/Akt signaling pathways | 第71-73页 |
| 4.5 Cordycepin and Illudin S docking to Fas and DR3 (TNFɑR) | 第73-74页 |
| CONCLUSIONS | 第74-75页 |
| NOVEL FINDINGS | 第75-76页 |
| Acknowledgements | 第76-77页 |
| REFERENCES | 第77-91页 |
| 在学期间公开发表论文及著作情况 | 第91页 |
