Dihydroartemisinin enhances doxorubicin-induced apoptosis of triple negative breast cancer cells by negatively regulating the STAT3/HIF-1α pathway.
10.12122/j.issn.1673-4254.2025.02.06
- Author:
Di CHEN
1
;
Ying LÜ
1
;
Yixin GUO
1
;
Yirong ZHANG
1
;
Ruixuan WANG
1
;
Xiaoruo ZHOU
1
;
Yuxin CHEN
1
;
Xiaohui WU
2
Author Information
1. School of Basic Medical Science, Xi'an Medical University, Xi'an 710021, China.
2. Xi'an Key Laboratory of Innovative and Translational Cancer Early Diagnosis, Xi'an Medical University, Xi'an 710021, China.
- Publication Type:Journal Article
- Keywords:
HIF-1α;
STAT3;
apoptosis;
dihydroartemisinin;
doxorubicin;
triple-negative breast cancer
- MeSH:
Humans;
STAT3 Transcription Factor/metabolism*;
Apoptosis/drug effects*;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*;
Doxorubicin/pharmacology*;
Triple Negative Breast Neoplasms/metabolism*;
Cell Line, Tumor;
Artemisinins/pharmacology*;
Female;
Cell Proliferation/drug effects*;
Signal Transduction/drug effects*;
Survivin
- From:
Journal of Southern Medical University
2025;45(2):254-260
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the effects of dihydroartemisinin (DHA) combined with doxorubicin (DOX) on proliferation and apoptosis of triple-negative breast cancer cells and explore the underlying molecular mechanism.
METHODS:MDA-MB-231 cells were treated with 50, 100 or 150 μmol/L DHA, 0.5 μmol/L DOX, or with 50 μmol/L DHA combined with 0.5 μmol/L DOX. The changes in proliferation and survival of the treated cells were examined with MTT assay and colony-forming assay, and cell apoptosis was analyzed with flow cytometry. Western blotting was performed to detect the changes in protein expression levels of PCNA, cleaved PARP, Bcl-2, Bax, STAT3, p-STAT3, HIF-1α and survivin.
RESULTS:The IC50 of DHA was 131.37±29.87 μmol/L in MDA-MB-231 cells. The cells with the combined treatment with DHA and DOX showed significant suppression of cell proliferation. Treatment with DHA alone induced apoptosis of MDA-MB-231 cells in a dose-dependent manner, but the combined treatment produced a much stronger apoptosis-inducing effect than both DHA and DOX alone. DHA at 150 μmol/L significantly inhibited clone formation of MDA-MB-231 cells, markedly reduced cellular expression levels of PCNA, p-STAT3, HIF-1α and survivin proteins, and obviously increased the expression level of cleaved PARP protein and the Bax/Bcl-2 ratio, and the combined treatment further reduced the expression level of p-STAT3 protein and increased the Bax/Bcl-2 ratio.
CONCLUSIONS:DHA combined with DOX produces significantly enhanced effects for inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 cells possibly as result of DHA-mediated negative regulation of the STAT3/HIF-1α pathway.
