Metformin 유도체 HL156A의 약물 다제내성 암세포 억제기전 규명
- Issued Date
- 2019
- Abstract
- Mutidrug-resistant is a significant clinical problem in the treatmnet of cancer and this resistance has been linked to the cellular expression of multidrug-efflux transporters. The aim of this study was to examine the effects and mechanisms of the new metformin derivative HL156A in human multidrug-resistant cancer cell lines (FADU/PTX, MCF7/ADR and SNU/CIP). HL156A significantly suppressed cell growth and colony formation in a concentration-dependent manner and caused G2/M phase arrest by inhibiting the expression of Cdk1/cyclin B1. HL156A also reduced wound closure/migration and induced cell death in multidrug-resistant cancer cells. We found that HL156A inhibited the expression of MDR1 through inhibiting of HOXC6-ERK1/2 signaling pathway. In addition, treatment of non-lethal dose 20 uM HL156A increased their sensitivity to paclitaxel or doxorubicin in FADU/PTX and MCF7/ADR. Furthermore, the anti-angiogenesis activity of HL156A was verified in chicken chorioallantoic membranes (CAMs). HL156A significantly inhibited angiogenesis in a CAM assay. These results suggest the potential value of the new metformin derivative HL156A as a candidate for a therapeutic modality for the treatment of multidrug resistance cancers.
- Alternative Title
- Metformin derivative HL156A, reverses multidrug resistance through inhibiting HOXC6/ERK1/2 signaling in human multidrug-resistant cancer cells
- Alternative Author(s)
- Jeong Yun Soo
- Department
- 일반대학원 치의생명공학과
- Advisor
- 안상건
- Awarded Date
- 2019-08
- Table Of Contents
- TABLE OF CONTENTS..........................................................................i
LIST OF FIGURES................................................................................iii
ABBREVIATIONS.................................................................................iv
ABSTRACT..........................................................................................v
I. 서 론.................................................................................................1
II. 실험재료 및 방법................................................................................4
2.1. Cell culture and reagents.......................................................4
2.2. Cell proliferation assay (MTT assay)........................................4
2.3. Soft agar colony formation assay............................................5
2.4. Wound healing motility assay.................................................5
2.5. Migration assay (Transwell assay)...........................................6
2.6. Cell cycle analysis...................................................................6
2.7. Annexin V-FITC / Propidium iodide(PI) double staining (Flow cytometry assay)..............................7
2.8. Annexin V-FITC / Propidium iodide(PI) double staining (Fluorescence microscopy assay)................7
2.9. Western blot analysis.............................................................8
2.10. RNA isolation and RT-PCR analysis........................................8
2.11. Quantitative real-time PCR...................................................9
2.12. HOAC6 Transfection...........................................................10
2.13. siRNA interference assay.......................................................10
2.14. Rhodamine accumulation assay............................................10
2.15. Chorioallantoic membrane(CAM) assay................................11
2.16. Statistical analysis.................................................................11
III. 실험결과..........................................................................................12
3.1. HL156A의 세포증식 억제효과..................................................12
3.2. HL156A가 세포주기에 미치는 영향...........................................17
3.3. HL156A의 migration과 invasion 억제효과................................20
3.4. HL156A의 세포 사멸 효과........................................................22
3.5. HOXC6와 MDR1의 발현에 HL156A가 미치는 영향.....................24
3.6. HOXC6, MDR1, ERK1/2의 경로 확인........................................27
3.6. HL156A의 세포내 약물 축적유도 및 약물 민감도 증가....................29
3.6. HL156A가 angiogenesis에 미치는 영향......................................32
IV. 고찰 및 결과.....................................................................................34
V. 참고문헌...........................................................................................38
VII. ACKNOWLEDGMENTS....................................................................
- Degree
- Master
- Publisher
- 조선대학교 일반대학원
- Citation
- 정연수. (2019). Metformin 유도체 HL156A의 약물 다제내성 암세포 억제기전 규명.
- Type
- Dissertation
- URI
- https://oak.chosun.ac.kr/handle/2020.oak/13919
http://chosun.dcollection.net/common/orgView/200000267380
- Appears in Collections:
- General Graduate School > 3. Theses(Master)
- Files in This Item:
-
-
Download
Metformin 유도체 HL156A의 약물 다제내성 암세포 억제기전 규명.pdf
기타 데이터 / 1.06 MB / Adobe PDF
-
Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.