The effect and mechanism of dihydroartemisinin on triple-negative breast cancer MDA-MB-231 cells / 西安交通大学学报(医学版)

ABSTRACT

【Objective】 To study the inhibitory effect of dihydroartemisinin （DHA） on triple negative breast cancer MDA-MB-231 cells and its mechanisms. 【Methods】 CCK-8 method was used to detect the inhibitory effects of DHA， artemisinin derivative， on the proliferation of triple negative breast cancer MDA-MB-231 cells. qRT-PCR and Western blot were used to test the expressions of CIZ1， Snail and TGF-β1 at mRNA and protein levels. After the exogenous application of TGF-β1 cytokines or TGF-β1 pathway inhibitor SD-208， Wound healing， Transwell invasion assay and Western blotting were performed to detect the effects of activation/inhibition of TGFβ1-smads pathway on the anti-metastatic effects of DHA and its mechanisms. 【Results】 DHA could significantly inhibit the proliferation of human breast cancer MDA-MB-231 cell lines in a dose-dependent manner. It could significantly suppress CIZ1， Snail， and TGF-β1 expressions at mRNA and protein levels in MDA-MB-231 cells. TGF-β1 cytokines treatment could enhance the migration and invasion ability of breast cancer cell， where TGF-β1 treatment also enhanced CIZ1， snail protein expression and smad2/3 protein phosphorylation level. DHA could reverse the above TGFβ1-induced effects. Furthermore， after the application of the TGF-β1 pathway inhibitor SD-208， the anticancer activity of DHA was enhanced， and the expressions of CIZ1， snail and phos-smad2/3 proteins were significantly inhibited. 【Conclusion】 DHA could significantly inhibit the proliferation and metastasis of breast cancer cells through suppressing the TGF-β1/Smad and CIZ1 signaling.