| ENGLISH ABSTRACT | 第1-9页 |
| CHINESE ABSTRACT | 第9-11页 |
| ABBREVIATIONS AND KEY WORDS | 第11-13页 |
| INTRODUCTION | 第13-22页 |
| MATERIALS | 第22-26页 |
| 1 Chemicals and agents | 第22页 |
| 2 Cell lines | 第22-23页 |
| 3 Antibodies and enzymes | 第23页 |
| 4 Solution preparation | 第23-26页 |
| METHODS | 第26-37页 |
| 1 Cell culture and reagent exposure | 第26页 |
| 2 Determination of cell proliferation | 第26页 |
| 3 Apoptosis determination by Hoechst 33258 staining | 第26-27页 |
| 4 Apoptosis determination by ELISA | 第27页 |
| 5 Apoptosis determination by TUNEL assay | 第27-28页 |
| 6 Protein amount determination | 第28页 |
| 7 Western blotting | 第28-29页 |
| 8 DNA isolation | 第29-30页 |
| 9 Determination of yield, purity of DNA | 第30-31页 |
| 10 Incorporation of Pt | 第31-32页 |
| 11 EGFR isolation | 第32-33页 |
| 12 EGFR autophosphorylation determination | 第33-34页 |
| 13 Anti-Src antibody purification and concentration | 第34页 |
| 14 Determination of tyrosine kinase activity of isolated v-Src | 第34-35页 |
| 15 Determination of protein kinase A | 第35-36页 |
| 16 Determination of protein kinase C | 第36-37页 |
| RESULTS | 第37-77页 |
| Part 1. The cytotoxic effects of β-HIVS on different cell lines | 第37-41页 |
| 1 Inhibitory effect of β-HIVS on BCR-Ab1-positive leukemia K562 cells | 第37-38页 |
| 2 Cytotoxicity of β-HIVS on BCR-Ab1-negative, monocyte-like, histiocytic lymphoma cells U937 cells | 第38页 |
| 3 Growth inhibition of β-HIVS on solid tumor cells- small cell lung carcinoma DMS114 cells | 第38-39页 |
| 4 β-HIVS inhibit the growth of the cells expressed high levels of tyrosine kinases | 第39-41页 |
| Part 2. The mechanisms of β-HIVS | 第41-47页 |
| 1 The inhibition of β-HIVS on tyrosine kinase activities | 第41-46页 |
| (1) High concentration of β-HIVS inhibited phosphorylation of BCR-Ab1 | 第42-44页 |
| (2) β-HIVS inhibited tyrosine kinase activity of v-Src | 第44页 |
| (3) β-HIVS inhibited autophosphorylation of EGFR | 第44-46页 |
| 2 The influences of β-HIVS on protein kinase A and C | 第46-47页 |
| (1) Effect of β-HIVS on protein kinase A | 第46页 |
| (2) Effect of β-HIVS on protein kinase C | 第46-47页 |
| Part 3. Combined effects of β-HIVS and chemotherapeutic agents on leukemia U937 cells and solid tumor DMS114 cells | 第47-57页 |
| 1 Screening of synergistic effects of β-HIVS with chemotherapeutic agents on U937 cells | 第48-52页 |
| (1) The isobologram | 第48-49页 |
| (2) Combined effects of β-HIVS with bufalin, VP16, Dox or CDDP on U937 cells | 第49-52页 |
| 2 Screening of synergistic effects of β-HIVS with chemotherapeutic agents on DMS114 cells | 第52-56页 |
| (1) Combined effect of β-HIVS and bufalin | 第52-53页 |
| (2) The influence of β-HIVS and VP16 together | 第53页 |
| (3) Effects of β-HIVS and Dox | 第53-56页 |
| 3 The synergistic effects of β-HIVS and CDDP on the growth of DMS114 cell | 第56-57页 |
| Part 4. The mechanism of synergistic effects of β-HIVS and CDDP on DMS114 cells | 第57-71页 |
| 1 Apoptosis induction of β-HIVS and CDDP together | 第57-60页 |
| (1) Apoptosis determination by ELISA | 第57-58页 |
| (2) Apoptosis determination by TUNEL assay | 第58-60页 |
| 2 Effects of β-HIVS on the accumulation of Pt content in cells, nuclei and DNA | 第60-63页 |
| 3 Effects of combination of β-HIVS and CDDP on MAP kinase | 第63-68页 |
| (1) Effect of combination of β-HIVS and CDDP on ERK1/2 kinases | 第63-64页 |
| (2) Effects of MEK inhibitor on the cell growth treated by combination | 第64页 |
| (3) Effect of combination of β-HIVS and CDDP on p38 kinase | 第64-66页 |
| (4) Effect of p38 MAP kinase inhibitor on the cell growth | 第66页 |
| (5) Effect of combination of β-HIVS and CDDP on JNK1/2 kinases | 第66-68页 |
| 4 The combination influenced tyrosine kinase activities | 第68-71页 |
| (1) In combination, β-HIVS and CDDP has a synergistic inhibitory effects on tyrosine kinase | 第68页 |
| (2) Combination effect of β-HIVS and CDDP on v-Src activity | 第68-69页 |
| (3) Combination effect of β-HIVS and CDDP on EGFR activity | 第69-71页 |
| Part 5. The synergistic effects of β-HIVS and trans-DDP on A431 cells | 第71-77页 |
| 1 Combination of trans-DDP and β-HIVS inhibit the growth of A431 cells | 第72-74页 |
| 2 The mechanism of synergistic effects of β-HIVS and trans-DDP on A431 cells | 第74-77页 |
| (1) Combined effect on isolated v-Src activity | 第74-75页 |
| (2) Combined effect on isolated EGFR activity | 第75-77页 |
| DISCUSSION | 第77-90页 |
| REFERENCES | 第90-108页 |
| ACKNOWLEDGEMENTS | 第108-109页 |
| PUBLICATIONS | 第109-110页 |
