Regulation of immune reactivity of ginsenoside and verification of anti-tumor effect based on pancreatic ductal adenocarcinoma
- 주제(키워드) 도움말 Pancreatic ductal adenocarcinoma , Ginsenoside
- 발행기관 강릉원주대학교 일반대학원
- 지도교수 도움말 이대희
- 발행년도 2024
- 학위수여년월 2025. 2
- 학위명 석사
- 학과 및 전공 도움말 일반대학원 KIST강릉분원학.연협동과정
- 세부분야 해당없음
- 실제URI http://www.dcollection.net/handler/kangnung/000000011997
- UCI I804:42001-000000011997
- 본문언어 영어
초록/요약 도움말
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with significant metastatic potential and a complex network of mechanisms that promote its proliferation and growth, presenting a major challenge in therapeutic research. Current treatments for PDAC are either associated with high toxicity and resistance or exhibit limited tumor responsiveness, resulting in a 5-year survival rate of less than 20% for PDAC patients. To overcome these limitations, there is a growing interest in the development of natural product-derived therapeutics. Among various natural compounds, ginsenosides have garnered significant attention for their potent anticancer effects across multiple types of cancer. Ginsenosides (GS) are a class of saponins and represent the principal bioactive components of ginseng (Panax ginseng), a medicinal plant that has been highly valued in East Asia for thousands of years. Notably, ginsenosides have been reported to induce tumor cell apoptosis and arrest the cell cycle, thereby inhibiting tumor growth. Furthermore, they have been studied as adjuvants capable of enhancing tumor responsiveness to immunotherapy. However, the anticancer effects of ginsenosides in pancreatic cancer have been scarcely reported. Therefore, this study aimed to identify novel ginsenoside derivatives with anti-tumor activity and immunomodulatory effects in PDAC model. To validate the effects of the selected ginsenoside derivatives, four candidates (GS1, GS2, GS3, GS4) were tested using a mouse PDAC cell line (Panc02) and primary mouse splenocytes. Apoptosis and cell cycle arrest in Panc02 cells were analyzed via flow cytometry. Immune cell activation was evaluated by measuring cytokine production (IFN-γ, TNF-α, IL-10) in splenocytes co-cultured with the ginsenoside derivatives under Treg-inducing conditions, which mimic the tumor immune microenvironment. Furthermore, the antitumor effects of GS3 and GS4, selected through in vitro experiments, were validated using a PDAC heterotopic mouse. The results showed that GS4 induced apoptosis and cell cycle arrest in Panc02 cells. GS3 enhanced TNF-α production in CD4+ and CD8+ T cells, suggesting its potential to stimulate antitumor immune responses. In a syngeneic mouse model of PDAC, GS3 improved cancer-associated cachexia, as evidenced by increased grip strength and muscle mass. In conclusion, ginsenoside derivatives, particularly GS3 and GS4, may represent promising therapeutic candidates for PDAC. Further research is needed to fully elucidate their mechanisms of action and to evaluate their therapeutic potential in combination with existing therapies.
more목차 도움말
Abstract i
국문 초록 iv
Abbreviations vii
List of Figures xi
1. INTRODUCTION 1
2. MATERIALS AND METHODS 7
2.1. Preparation of GS 7
2.2. Cell culture and maintenance 7
2.3. Optimization of cell culture condition 7
2.4. Apoptosis assay 8
2.5. Cell cycle arrest assay 8
2.6. Animals 9
2.7. Isolation of lymphocytes 9
2.8. Immune cell screening 10
2.9. In vivo PDAC heterotopic model 11
2.10. Grip strength measurement 12
2.11. Cytokine analysis 12
2.12. Flow cytometry analysis 13
2.13. Statistical analysis 14
3. RESULTS 15
3.1. Anti-tumor effects of ginsenosides in Panc02 cells. 15
3.2. Effects of ginsenosides on cytokine production in lymphocytes 24
3.3. GS treatment did not affect body weight and tumor burden 31
3.4. Effect of GS on cancer-associated cachexia in PDAC heterotopic model 36
3.5. Modulation of immune responses by ginsenosides in the tumor immune environment 44
4. DISCUSSION 53
5. Refrence 58
