Effect of Rotundic Acid on Hepatocellular Carcinoma and Its
发布时间：2023-02-19 13:14
根据国际癌症研究协会(IARC)发表的报告,肝癌总体上在发病率方面排名第六,是癌症相关死亡的第四大原因。在其治疗方面,如果手术不是一种选择,可以通过靶向药物治疗来控制HCC的蔓延。由于肝脏恶性肿瘤通常在其晚期阶段被检测,因此该疾病是非常致命的,并且在这些阶段单独或与其他治疗模式联合化疗仍然是在HCC中提供生存益处的最佳可能方式。在过去的20年中,索拉非尼和雷戈拉非尼是FDA批准的用于肝癌治疗的化学制剂。虽然这些靶向药物已经适度地改善了中间生存期,但它们未能产生可持续的生存效益。目前化疗药物的疗效有限,缺乏持久反应,迫切需要开发新的和现代的治疗药物,以提高治疗反应和最小化对HCC患者的毒性。救必应酸(RA)是一种植物来源的三萜类化合物,文献报道具有抗炎和心脏保护作用。虽然RA及其衍生物可以通过凋亡诱导多种肿瘤细胞死亡,但RA对肝癌的作用及其作用机制尚不清楚。本文重点研究了RA在体外和体内条件下对肝癌的抗癌作用。MTT,细胞迁移和侵袭实验表明,RA可成功抑制Hep G2,SMMC-7721,和内皮HUVEC细胞的细胞活力,增殖和迁移潜力。通过软琼脂集落形成和克隆形成实验确定RA对HCC细胞...
【文章页数】：108 页
【学位级别】：博士
【文章目录】：
Abstract (English)
Abstract (Chinese)
List of abbreviations
Chapter 1: Introduction and review of literature#1 -
1.1. Cancer
1.2. Hepatocellular carcinoma (HCC)
1.3. Hepatocellular carcinoma and angiogenesis
1.4. Available treatment options for HCC
1.5. Chemotherapy
1.5.1. Alkylating agents
1.5.2. Antimetabolites
1.5.3. Anti-tumor antibiotics
1.5.4. Topoisomerase inhibitors
1.5.5. Vinka alkaloids
1.5.6. m TOR inhibitors
1.5.7. Kinase inhibitor drugs
1.5.8. Neo-adjuvant chemotherapy
1.5.9. Concomitant Chemo-radiotherapy
1.5.10. Adjuvant chemotherapy
1.6. Novel therapeutics
1.6.1. Targeting Epidermal Growth Factor Receptor in HCC
1.6.2. Targeting Ras in HCC
1.6.3. Targeting p53 in HCC
1.7. Apoptosis
1.8. Apoptosis: A target for cancer therapy
1.9. Major cell death and survival pathways in cancer
1.10. Apoptosis regulators
1.10.1. Caspase
1.10.2. Bcl-2 family of proteins
1.10.3. Cytochrome c
1.10.4. NFκ B
1.10.5. VEGF
1.11. Rotundic acid (RA)
Chapter 2: Materials and reagents
2.1. Materials
2.2. Reagents
Chapter 3: Experimental methodologies and protocols
3.1. Cell culture and maintenance of cell lines
3.1.1. Revival of cell lines
3.1.2. Passaging cells
3.1.3. Cell seeding
3.1.4. Hemocytometer calculations
3.1.5. Cryopreservation
3.2. Drug dilutions and treatments
3.3. Cell viability assay
3.4. Colony formation assay
3.5. Anchorage-independent soft agar colony formation assay
3.6. Migration assays
3.7. Invasion assay
3.8. Gelatin zymography
3.9. Cell cycle assay
3.10. DNA damage
3.11. Annexin V-FITC/PI staining
3.12. Tube formation assay
3.13. Immunoblotting
3.14. VEGF-ELISA
3.15. Tumor xenograft study
3.16. CD-31 and TUNEL staining (IHC)
3.17. Statistical analtsis
Chapter 4: Results
4.1. Effect of Rotundic acid on the cell viability and proliferation of Hepatocellularcarcinoma cells
4.2. Effect of Rotundic acid on the migration and invasion of Hepatocellular carcinomacells
4.3. Effect of Rotundic acid on the MMP secretion in HCC cells
4.4. Rotundic acid induces S-phase cell cycle arrest in Hep G2 cells
4.5. Rotundic acid induces apoptosis in Hep G2 cells
4.6. Effects of RA on endothelial HUVEC cells
4.7. RA inhibits HCC by modulating AKT/m TOR and MAPK pathways
4.8. Effects of RA on tumor xenograft mice model of hepatocellular carcinoma
Chapter 5: Discussion and conclusion
References
攻读博士学位期间取得的研究成果
List of publications
Acknowledgements
附件
本文编号：3746289
【文章页数】：108 页
【学位级别】：博士
【文章目录】：
Abstract (English)
Abstract (Chinese)
List of abbreviations
Chapter 1: Introduction and review of literature#1 -
1.1. Cancer
1.2. Hepatocellular carcinoma (HCC)
1.3. Hepatocellular carcinoma and angiogenesis
1.4. Available treatment options for HCC
1.5. Chemotherapy
1.5.1. Alkylating agents
1.5.2. Antimetabolites
1.5.3. Anti-tumor antibiotics
1.5.4. Topoisomerase inhibitors
1.5.5. Vinka alkaloids
1.5.6. m TOR inhibitors
1.5.7. Kinase inhibitor drugs
1.5.8. Neo-adjuvant chemotherapy
1.5.9. Concomitant Chemo-radiotherapy
1.5.10. Adjuvant chemotherapy
1.6. Novel therapeutics
1.6.1. Targeting Epidermal Growth Factor Receptor in HCC
1.6.2. Targeting Ras in HCC
1.6.3. Targeting p53 in HCC
1.7. Apoptosis
1.8. Apoptosis: A target for cancer therapy
1.9. Major cell death and survival pathways in cancer
1.10. Apoptosis regulators
1.10.1. Caspase
1.10.2. Bcl-2 family of proteins
1.10.3. Cytochrome c
1.10.4. NFκ B
1.10.5. VEGF
1.11. Rotundic acid (RA)
Chapter 2: Materials and reagents
2.1. Materials
2.2. Reagents
Chapter 3: Experimental methodologies and protocols
3.1. Cell culture and maintenance of cell lines
3.1.1. Revival of cell lines
3.1.2. Passaging cells
3.1.3. Cell seeding
3.1.4. Hemocytometer calculations
3.1.5. Cryopreservation
3.2. Drug dilutions and treatments
3.3. Cell viability assay
3.4. Colony formation assay
3.5. Anchorage-independent soft agar colony formation assay
3.6. Migration assays
3.7. Invasion assay
3.8. Gelatin zymography
3.9. Cell cycle assay
3.10. DNA damage
3.11. Annexin V-FITC/PI staining
3.12. Tube formation assay
3.13. Immunoblotting
3.14. VEGF-ELISA
3.15. Tumor xenograft study
3.16. CD-31 and TUNEL staining (IHC)
3.17. Statistical analtsis
Chapter 4: Results
4.1. Effect of Rotundic acid on the cell viability and proliferation of Hepatocellularcarcinoma cells
4.2. Effect of Rotundic acid on the migration and invasion of Hepatocellular carcinomacells
4.3. Effect of Rotundic acid on the MMP secretion in HCC cells
4.4. Rotundic acid induces S-phase cell cycle arrest in Hep G2 cells
4.5. Rotundic acid induces apoptosis in Hep G2 cells
4.6. Effects of RA on endothelial HUVEC cells
4.7. RA inhibits HCC by modulating AKT/m TOR and MAPK pathways
4.8. Effects of RA on tumor xenograft mice model of hepatocellular carcinoma
Chapter 5: Discussion and conclusion
References
攻读博士学位期间取得的研究成果
List of publications
Acknowledgements
附件
本文编号：3746289
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