Corosolic Acid Targets and Modulates the TGF-β1/SMAD2/3 Pathway to Inhibit Melanoma Proliferation and Metastasis
10.11969/j.issn.1673-548X.2025.04.021
- VernacularTitle:科罗索酸靶向调节TGF-β1/SMAD2/3通路抑制黑色素瘤增殖和转移
- Author:
Wennan LI
1
;
Xiaoli WANG
1
Author Information
1. 712000 咸阳,陕西中医药大学附属医院皮肤科
- Publication Type:Journal Article
- Keywords:
Corosolic acid;
Melanoma;
Proliferation;
Metastasis;
TGF-β1;
SMAD2/3
- From:
Journal of Medical Research
2025;54(4):116-121
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the therapeutic effect of corosolic acid on melanoma and its possible molecular mechanisms.Methods Melanoma B16 cells and A375 cells were cultured and divided into control group(0μmol/L),low concentration corosolic acid group(5μmol/L),medium concentration corosolic acid group(10μmol/L),and high concentration corosolic acid group(20μmol/L).According to the grouping,the two types of cells were intervened with corresponding concentrations of corosolic acid.Then,the cell prolif-eration activity was detected by colony formation assay,the cell migration ability was detected by scratch assay,and the cell invasion abili-ty was detected by Transwell assay.Western blot analysis was performed to detect the expression levels of transforming growth factor-β1(TGF-β1),mothers against DPP hom 2(Drosophila)(SMAD2),SMAD3,phosphorylated SMAD2(p-SMAD2),phosphorylated SM3(p-SMAD3),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X(Bax),and Bcl-2 associated death promoter(Bad)in cells.Immunofluorescence staining was used to detect the expression levels of N-cadherin and Vimentin in cells.For response experi-ments,TGF-β1 recombinant protein was added to the cell culture system of the corosamic acid treated groups as described above.Results Compared with the blank group cells,intervention with different concentrations of corosolic acid significantly inhibited the prolif-eration,migration,and invasion activities of B16 cells and A375 cells,showing a concentration-dependent effect.Additionally,corosol-ic acid intervention led to a significant decrease in the expression levels of TGF-β1,p-SMAD2,p-SMAD3,Bcl-2,N-cadherin,and Vimentin proteins within melanoma cells,while significantly increasing the expression levels of Bax and Bad proteins.However,there was no significant change in the expression levels of SMAD2 and SMAD3 proteins.After adding recombinant TGF-β1 protein,the inhibi-tory effect of corosolic acid on melanoma cells was partially reversed.Conclusion Corosolic acid can significantly inhibit the prolifera-tion,migration,and invasion activities of melanoma cells,and this is related to its inhibition of the TGF-β1/SMAD2/3 pathway.