Berberine Reverses Hypoxia-induced Chemoresistance in Breast Cancer through the Inhibition of AMPK- HIF-1α
| Autor: | Kan He, Yawei Zhao, Yong-Fei Tan, Li Chen, Yue Pan, Dan Shao, Jing Li, Fan Zhang, Xiao Zheng |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
AMPK Berberine breast cancer resistance Cell AMP-Activated Protein Kinases Applied Microbiology and Biotechnology chemistry.chemical_compound Mice 0302 clinical medicine AMP-activated protein kinase Chemosensitization Medicine Mice Inbred BALB C biology HIF-1α Cell Hypoxia Gene Expression Regulation Neoplastic medicine.anatomical_structure 030220 oncology & carcinogenesis MCF-7 Cells Female medicine.symptom Research Paper Mice Nude Antineoplastic Agents Breast Neoplasms 03 medical and health sciences Breast cancer Cell Line Tumor Animals Humans Molecular Biology Ecology Evolution Behavior and Systematics business.industry hypoxia Cell Biology Hypoxia (medical) medicine.disease Hypoxia-Inducible Factor 1 alpha Subunit 030104 developmental biology chemistry Apoptosis Drug Resistance Neoplasm biology.protein Cancer research business Developmental Biology |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| Popis: | Breast cancer is the most common type of cancer and the second leading cause of cancer death in American women. Chemoresistance is common and inevitable after a variable period of time. Therefore, chemosensitization is a necessary strategy on drug-resistant breast cancer. In this study, MCF-7 breast cancer cell was cultured under hypoxia for a week to induce the resistance to doxorubincin (DOX). The effect of different doses of berberine, a traditional Chinese medicine, on DOX sensitivity to MFC-7/hypoxia cells was observed. We found that hypoxia increased DOX resistance on breast cancer cells with the AMPK activation. Low-dose berberine could resensitize DOX chemosensitivity in MCF-7/hypoxia cell, however, high-dose berberine directly induced apoptosis. The intriguing fact was that the protein expressions of AMPK and HIF-1α were down-regulated by berberine, either low dose or high dose. But the downstream of HIF-1α occurred the bifurcation dependent on the dosage of berberine: AMPK-HIF-1α-P-gp inactivation played a crucial role on the DOX chemosensitivity of low-dose berberine, while AMPK-HIF-1α downregulaton inducing p53 activation led to apoptosis in high-dose berberine. These results were consistent to the transplanted mice model bearing MCF-7 drug-resistance tumor treated by berberine combined with DOX or high-dose berberine alone. This work shed light on a potentially therapeutic attempt to overcome drug-resistant breast cancer. |
| Databáze: | OpenAIRE |
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