| Abstract | 第6-7页 |
| Chapter 1 Drug Resistance, Classification, Mechanism and Novel Approaches for Suppressing Cancer and Overcoming Undruggable Drug Resistance | 第11-32页 |
| 1.1 Introduction | 第11-30页 |
| 1.1.1 Explanation and molecular mechanism underlying the development of drug resistance | 第13-15页 |
| 1.1.2 Development of drug resistance in response to inhibitors | 第15-17页 |
| 1.1.3 Tumor Response and Clonal Evolution in Response to Chemotherapy | 第17-19页 |
| 1.1.4 Role of rent tumor gatekeeper in cancer suppression | 第19-24页 |
| 1.1.5 New Strategies for drugging undrugable drug resistance | 第24-30页 |
| Conclusion | 第30-32页 |
| Chapter 2 Drugging Reppressed Chromatin: Communication between Enhancers and Transcriptional Factors Suppresses Cancer Development and Increases Gene Transcription through Chromatin Accessibility | 第32-59页 |
| 2.1 Introduction | 第32-58页 |
| 2.1.1 Features of Active Enhancers | 第34-36页 |
| 2.1.2 Role of Epigenetic Modifications in the Suppression of Tumor | 第36-39页 |
| 2.1.3 Function of Transcriptional Factors in Transcriptional Regulation | 第39-40页 |
| 2.1.4 Communication between Enhancers and Transcriptional Factors is required for Gene Regulation | 第40-42页 |
| 2.1.5 Communication between Transcriptional Factors and Enhancers Increases Gene Transcription and Suppresses Tumor | 第42-51页 |
| 2.1.6 The Perturbed Expression of Transcriptional Factors Reduces Gene Transcription and Increases the Expression of Oncogenes | 第51-53页 |
| 2.1.7 eRNA Transcripts trap more Target Genes and Facilitates Looping between Enhancer and Promoter | 第53-58页 |
| Future Direction | 第58-59页 |
| Chapter 3 Expression, Crystallization and Preliminary X-ray Diffraction Analyses of Med-ORF10 in the Biosynthetic Pathway of an Antitumor Antibiotic Medermycin | 第59-71页 |
| 3.1 Introduction | 第59-61页 |
| 3.2 Materials and Methods | 第61-63页 |
| 3.2.1. Strains and Plasmids | 第61页 |
| 3.2.2. Gene Cloning | 第61-62页 |
| 3.2.3. Protein Expression | 第62页 |
| 3.2.4. Protein Purification | 第62页 |
| 3.2.5. Protein Crystallization | 第62-63页 |
| 3.2.6. X-ray Diffraction and Data Collection | 第63页 |
| 3.2.7. Expression Detection of Med-ORF10 in its Native Wild Type Strain | 第63页 |
| 3.3. Results | 第63-69页 |
| 3.3.1. Protein Expression and Purification | 第63-66页 |
| 3.3.2. Protein Crystallization and X-ray Diffraction | 第66-68页 |
| 3.3.3. Flag-Tagged-Med-ORF10 was Expressed in Streptomyces Successfully | 第68-69页 |
| 3.4. Discussions | 第69-71页 |
| Chapter 4 Overeapression of SPRYD4 suppresses cancer progression through modulating mitochondrial dynamics | 第71-98页 |
| 4.1 Introduction | 第71-76页 |
| 4.2. Materials and Methods | 第76-85页 |
| 4.2.1 Preparation of reagents used for experiment | 第76-78页 |
| 4.2.2. SDS PAGE & Western Blot | 第78-79页 |
| 4.2.3. Gene cloning | 第79页 |
| 4.2.4. Recovery and purification of PCR product | 第79-82页 |
| 4.2.5. Cell culture and transfection | 第82页 |
| 4.2.6. SDS-PAGE | 第82-83页 |
| 4.2.7. Western blot analysis | 第83-84页 |
| 4.2.8. Cell viability assay | 第84页 |
| 4.2.9. ATP assay | 第84页 |
| 4.2.10. Lactate Production and Glucose Uptake Analysis | 第84-85页 |
| 4.2.11. Mitochondrial image processing and confocal microscopy | 第85页 |
| 4.3. Results | 第85-96页 |
| 4.3.1. Amplification and expression pattern analysis of SPRYD4 | 第85-86页 |
| 4.3.2. Overexpression of SPRYD4 decreased mitochondrial fragmentation in HeLa cells | 第86-90页 |
| 4.3.3. Overexpression of SPRYD4 suppresses cancer cell proliferation and energy production | 第90-92页 |
| 4.3.4. Overexpression of SPRYD4 suppresses cancer cell glycolysis | 第92-93页 |
| 4.3.5. Loss of SPRD4 compromises mitochondrial fragmentation | 第93-96页 |
| 4.4. Discussion | 第96-98页 |
| Chapter 5 Anticancer agent FL3 inhibits cancer cell proliferation through impairing energy metabolism and inducing cell cycle arrest | 第98-105页 |
| 5.1 Introduction | 第98-99页 |
| 5.2 Materials and methods | 第99-100页 |
| 5.2.1 Reagents and Cell Culture | 第99页 |
| 5.2.2 ATP assay | 第99页 |
| 5.2.3 Lactate Production and Glucose Uptake Analysis | 第99-100页 |
| 5.2.4 Western Blot Analysis | 第100页 |
| 5.2.5 Statistical Analysis | 第100页 |
| 5.3 Results | 第100-105页 |
| 5.3.1 FL3 selectively suppresses the growth of cancer cells through inducing cell cycle arrest and inhibiting energy production | 第100-103页 |
| 5.3.2 FL3 suppresses cancer cell glycolysis | 第103-105页 |
| References | 第105-128页 |
| 附件 | 第128-129页 |
| Publications | 第129-130页 |
| Acknowledgement | 第130-131页 |
