Effect and mechanism of hesperetin on P-selectin mediated breast cancer MDA-MB-231 metastasis / 中草药

ABSTRACT

Objective: To study the effect of hesperetin on the migration of P-selectin mediated MDA-MB-231 breast cancer cells and its mechanism. Methods: Using computer virtual docking to evaluate the capacity of hesperetin binding to P-selectin in vitro; MTS test was observed with different concentration of hesperetin or P-selectin on the growth capacity of MDA-MB-231; The effect of hesperetin on P-selectin secretion by activated platelet was detected by Elisa kit; Adhesion experiments examined hesperetin on P-selectin-mediated MDA-MB-231 and endothelial cell adhesion; Transwell experiment was performed to analyze the effect of P-selectin on MDA-MB-231 breast cancer cell migration affected by hesperetin; Western blotting investigated MDA-MB-231 cell surface glycoprotein Mucin-1, Integrin β3, β1 and matrix metalloproteinase expression of MMP-2 and MMP-9 protein expression influenced by hesperetin; impact of hesperetin on MDA-MB-231 cell integrin-matrix metalloproteinase signaling pathway was analyzed to clarify the anti-tumor metastasis mechanism of hesperetin. Results: Hesperetin inhibited P-selectin-induced MDA-MB-231 cell migration and reduced HUVEC-breast cancer cell adhesion. Hesperetin down-regulated the expression of β1 and β3 integrins, and MMP-2 and MMP-9 at protein levels in MDA-MB-231 cells. Conclusion: Hesperetin can inhibit the growth capacity of MDA-MB-231 breast cancer cells, block P-selectin-induced breast cancer MDA-MB-231 tumor cell migration and adhesion, and the mechanism for hesperetin is through competitive P-selectin binding to Mucin-1.Subsequently, hesperetin could block PI3K/AKT/Paxillin/FAK/Src signaling pathway and down-regulate P-selectin mediated Integrins, MMP-2, and MMP-9 expression.