Dihydroartemisinin enhances doxorubicin-induced apoptosis of triple negative breast cancer cells by negatively regulating the STAT3/HIF-1α pathway
CHEN Di
LÜ Ying
GUO Yixin
ZHANG Yirong
WANG Ruixuan
ZHOU Xiaoruo
CHEN Yuxin
WU Xiaohui
Abstract：Objective 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.Conclusion 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.
Keywords：dihydroartemisinindoxorubicinSTAT3HIF-1αtriple-negative breast cancerapoptosis
Publication Date：2025-02-19
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 254-260 )