Study On The Mechanism Of Parthenolide In Regulating Src Signal Pathway To Inhibit HER-2 Positive Breast Cancer Cell Line SK-BR-3

Objective: To explore the mechanism of parthenolide in inhibiting HER-2 positive breast cancer cell line SK-BR-3.Methods:（1）The in vitro survival ability of HER-2 positive breast cancer cell line SK-BR3 treated with different concentrations of parthenolide was observed by CCK-8 assay,and the IC50 value of parthenolide was calculated.（2）EDU staining and colony formation assay were used to further observe the proliferation ability of SK-BR-3cells under the intervention of altered concentrations of parthenolide.（3）Flow cytometry was utilized to detect the changes of apoptosis and cell cycle of SK-BR-3 cells treated with parthenolide.（4）Western blot method was utilized to observe the changes of protein expression of Src,p-Src,Cdh1,STAT3,p-STAT3 and PD-L1 in breast cancer cells SK-BR-3treated with parthenolide.Results:（1）Parthenolide could inhibit the viability of breast cancer cell line SK-BR-3 in vitro.CCK-8 results showed that the viability of SK-BR-3 cells decreased significantly with the increase of concentration,and the IC50 value was 7.27μmol/L.（2）EDU staining and colony formation assay showed that the proliferation activity of SK-BR-3 cells decreased with the increase of parthenolide concentration.（3）Parthenolide could induce apoptosis of SK-BR-3 cells in vitro.The results of flow cytometry showed that different concentrations of parthenolide（5μmol/L,10μmol/L,15μmol/L）could induce apoptosis of SK-BR-3 cells,and the apoptosis rate increased with the increase of parthenolide concentration.（4）Parthenolide interferes with the cell cycle progression of SK-BR-3 by blocking S phase.（5）Parthenolide can down-regulate PD-L1 expression by regulating Src signal pathway,suggesting that the inhibitory mechanism of parthenolide on SK-BR-3cells may be linked to the regulation of Src/PD-L1.Conclusion: Parthenolide can significantly inhibit the proliferation of HER-2 positive breast cancer cell line SK-BR-3 and promote its apoptosis in vitro.The mechanism of action may be closely linked to the regulation of Src/PD-L1.