Regulatory Changes in AMPK-Mediated Metabolism in Drug-Resistant Colorectal Cancer
- 주제(키워드) AMPK , colorectal cancer , drug resistance , autophagy , metabolism , butyrate resistance , oxaliplatin resistance , PXR
- 주제(DDC) 651.1
- 발행기관 아주대학교 일반대학원
- 지도교수 김소희
- 발행년도 2026
- 학위수여년월 2026. 2
- 학위명 석사
- 학과 및 전공 일반대학원 바이오헬스규제과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000035612
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Resistance to both endogenous and exogenous substances, including chemotherapy, remains a major clinical challenge in colorectal cancer. Although AMP-activated protein kinase (AMPK) is a central metabolic regulator, its role in drug-resistant cancer cells is highly context-dependent. This study investigated how AMPK modulation influences autophagy, metabolism, and drug resistance in butyrate-resistant (BR) and oxaliplatin-resistant (OR) colorectal cancer cells by inducing AMPK overexpression in BR cells and AMPK knockdown in OR cells. In BR cells with suppressed AMPK activity, AMPK overexpression restored autophagic flux, normalized glucose and lipid metabolism, and reactivated apoptotic signaling, thereby reversing resistance. Conversely, OR cells with elevated AMPK activity exhibited reduced autophagy and enhanced glycolysis; AMPK inhibition reversed these alterations and increased chemosensitivity. Notably, AMPK modulation consistently reduced pregnane X receptor (PXR) expression in both cell types, suggesting that AMPK-dependent PXR suppression serves as a shared downstream mechanism contributing to improved chemosensitivity across distinct resistance states. This study provides mechanistic insight into the interplay between metabolic reprogramming, autophagic regulation, and chemoresistance. The consistent decrease in PXR expression following AMPK normalization highlights the AMPK–PXR axis as a key molecular node integrating metabolic homeostasis with drug-response pathways. These findings support incorporating AMPK–PXR targeting into precision-based therapeutic strategies and provide a mechanistic framework for developing resistance-tailored combination therapies in colorectal cancer.
more목차
I. INTRODUCTION 1
II. METHOD 3
A. Chemicals 3
B. Cell culture and establishment of transfection in butyrate resistance and oxaliplatin resistance colorectal cancer cells 4
C. Cell proliferation assay 5
D. Immunofluorescence analysis 6
E. RNA extraction and reverse transcription 7
F. Quantitative real-time reverse transcription PCR 7
G. Protein isolation and immunoblot analysis 9
H. Statistical analysis 10
III. RESULT 11
A. Verification of AMPK expression 11
B. AMPK overexpression restores chemosensitivity in butyrate-resistant colorectal cancer cells 13
C. AMPK inhibition restores chemosensitivity in oxaliplatin-resistant colorectal cancer cells 16
D. Effects of AMPK transfection on cell cycle progression in butyrate-resistant and oxaliplatin-resistant colorectal cancer cells 19
E. Effects of AMPK overexpression on autophagy in butyrate-resistant colorectal cancer cells 21
F. Effects of AMPK knockdown on autophagy in oxaliplatin-resistant colorectal cancer cells 24
G. Effects of AMPK transfection on AMPK and Akt/mTOR signaling pathways in butyrate-resistant and oxaliplatin-resistant colorectal cancer cells. 27
H. Effects of AMPK transfection on enzymes involved in fatty acid metabolism in butyrate- and oxaliplatin-resistant colorectal cancer cells 29
I. Effects of AMPK transfection on glucose metabolism in butyrate- and oxaliplatin-resistant colorectal cancer cells 31
J. Effects of AMPK transfection on drug transporter and metabolic enzyme in butyrate- and oxaliplatin-resistant colorectal cancer cells 33
IV. DISCUSSION 35
V. CONCLUSION 38
REFERENCES 40
KOREAN ABSTRACT 45
