鸦胆子醇提物抗三阴性乳腺癌机制研究OA

[Objective]To explore the therapeutic effect of Brucea javanica ethanol extract(BJ-EE)on triple-negative breast cancer(TNBC)and verify its possible mechanism of action.[Methods]The ability of BJ-EE to inhibit TNBC cell proliferation after 24 h was detected by CCK-8 assay.The long-term effect of BJ-EE on TNBC cell proliferation was evaluated by colony formation assay.Morphological changes of cells after BJ-EE treatment were observed using an inverted microscope.The in vivo efficacy of BJ-EE against TNBC was evaluated based on a 4T1 tumor-bearing mouse model.Transcriptomic sequencing analysis was performed on tumor tissues from 4T1 tumor-bearing mice to explore the potential mechanism of BJ-EE in TNBC treatment.The effect of BJ-EE on TNBC cell apoptosis was detected by flow cytometry.Apoptosis-related gene and protein changes were verified by quantitative real-time polymerase chain reaction(RT-qPCR)and Western blot.[Results]CCK-8 results showed that,compared with the control group,BJ-EE significantly inhibited the viability of 4T1 and MDA-MB-231 cells(P<0.05 or P<0.01)in a dose-dependent manner.Colony formation assays showed that BJ-EE could inhibit the long-term proliferation of 4T1 and MDA-MB-231 cells(P<0.01).Cell morphology changed significantly after BJ-EE treatment.In vivo,BJ-EE could also inhibit TNBC tumor growth.Transcriptomic sequencing suggested that the mechanism of action of BJ-EE against TNBC might be inducing apoptosis.Flow cytometry results confirmed that BJ-EE could induce apoptosis in TNBC cells.RT-qPCR detected upregulation of the apoptosis-related genes Bax and caspase-3,and downregulation of Bcl-2(P<0.05).Western blot results showed upregulation of the pro-apoptotic protein Bax and the nuclear transcription factor-κB(NF-κB),and downregulation of the anti-apoptotic protein Bcl-2(P<0.05).[Conclusion]Brucea javanica ethanol extract can inhibit TNBC by inducing apoptosis.