α- Mangostin에 의한 ER stress 조절을 통한 췌장암 세포의 젬시타빈 유도 세포 사멸 증진 효과
α- Mangostin enhances Gemcitabine-induced apoptosis via modulation of Endoplasmic Reticulum Stress in pancreatic cancer cells
- 주제(키워드) 도움말 Pancreatic Cancer , Gemcitabine , α-Mangostin , endoplasmic reticulum stress , apoptosis , UPR
- 발행기관 국립강릉원주대학교 일반대학원
- 지도교수 도움말 이대희
- 발행년도 2025
- 학위수여년월 2026. 2
- 학위명 석사
- 학과 및 전공 도움말 일반대학원 웰니스바이오산업학과
- 세부분야 해당없음
- 실제URI http://www.dcollection.net/handler/kangnung/000000012363
- UCI I804:42001-000000012363
- 본문언어 영어
초록/요약 도움말
Pancreatic cancer is a fatal malignancy with a poor prognosis, and the low response rate and development of drug resistance to the first-line chemotherapeutic agent, Gemcitabine, remain major clinical limitations to overcome. This study aimed to target the critical mechanism underlying Gemcitabine's limited efficacy, the Endoplasmic Reticulum (ER) stress response. We sought to explore the molecular mechanisms by which the natural compound α-Mangostin effectively enhances the anticancer sensitivity to Gemcitabine. We treated pancreatic cancer cell lines (BxPC-3 Luc, Panc-1, AsPC-1) with a combination of α-Mangostin and Gemcitabine. Cell proliferation and migration were assessed using WST assay, Crystal Violet assay, Wound healing assay. Apoptotic pathways were investigated by Flow Cytometry and Western Blotting analysis, specifically utilizing the ROS inhibitor (NAC) to Confirm the ROS-dependency of ER stress induction. The combination treatment significantly inhibited cell proliferation and migration compared to single treatments. The combination selectively shifted the Unfolded Protein Response (UPR) from a survival signal toward an apoptotic signal, markedly increasing Caspase-dependent cell death. Mechanistically, α-Mangostin amplified the expression of the ER stress apoptotic marker, the PERK/ATF4/CHOP axis. The NAC treatment results, which showed an increase in CHOP expression, demonstrated that the ER stress-mediated apoptotic signal operates ROS-independently. This enhanced apoptosis was ultimately driven by the downregulation of anti-apoptotic Bcl-2 and the reduction of the apoptosis inhibitor C-FLIP. α-Mangostin successfully enhanced Gemcitabine sensitivity through the ROS-independent modulation of the ER stress pathway. This suggests a promising new combination therapy strategy for pancreatic cancer to maximize efficacy while minimizing the toxicity of Gemcitabine.
more목차 도움말
Abstract 6
Ⅰ. Introduction 10
Ⅱ. Materials and Methods 13
2.1. Cell culture 13
2.2. Chemicals and Reagents 13
2.3. WST assay 14
2.4. Crystal Violet assay 14
2.5. Wound healing assay 14
2.6. Flow Cytometry Analysis 15
2.7. Western Blotting 16
2.8. Statistical analysis 16
Ⅲ. Results 18
3.1. Gemcitabine and α-Mangostin Inhibit Pancreatic Cancer Cell Proliferation in a Dose- and Cell-Dependent Manner 18
3.2. α-Mangostin Enhances Gemcitabine Chemosensitivity 22
3.3. Combination Treatment of Gemcitabine and α-Mangostin Inhibits Pancreatic Cancer Cell Migration 26
3.4. Combination Treatment Enhances Apoptosis and Initiates Extrinsic Apoptotic Cascade 29
3.5. α-Mangostin-Mediated Chemosensitivity Involves ER stress Induction Independently of ROS 33
Ⅳ. Conclusion 37
Ⅴ. References 40
