Brucine Inhibits Vasculogenic Mimicry Of Breast Cancer Cells And The Related Mechanism

Background and purpose: It is still an urgent problem to be solved that the recurrence and metastasis of breast cancer in the current clinical treatment.For the past few years,researchers have successively investigated that: The existence of Vasculogenic mimicry(VM)in a large variety of highly invasive tumors,such as breast cancer,hepatocellular carcinoma,gastric cancer,ovarian carcinoma,may lead to the clinical efficacy of traditional anti-angiotherapy can not be expected.Brucine,a natural plant alkaloid,isolated from the seeds of medicinal herb,Strychnos nux-vomica Linn.,has been widely used in treatment of various tumors.Previous research have proved it has the potential antiangiogenic effect.This study aimed to explore the effect of Brucine on vasculogenic mimicry formation of breast cancer cells MDA-MB-231 in vitro and the potential mechanisms.Methods: The inhibition effect of brucine on growth of MDA-MB-231 cells was measured by MTT method.Annexin V-FITC/PI binding assay was used to assay the apoptosis rate of MDA-MB-231 cells after different concentration of brucine treatment.HO/PI dual staining was used to assay cells death detection.A Three-dimensional system of breast cancer cells MDA-MB-231 on Matrigel collagen matrix was used to investigate whether breast cancer cells can develop vasculogenic mimicry,and to determine the effects of Brucine on this process.Furthermore,the expressions of the related marker protein molecules(VEGF?VE-cadherin?Eph A2?MMP-2?MMP-9)of VM were determined by Western blot.Results:(1)Brucine displayed significant anti-proliferative effect on MDA-MB-231 cells in a dose-and time-dependent manner.Brucine could significantly induced MDA-MB-231 cells apoptosis and necrosis,increased the death rate.(2)A Three-dimensional system of breast cancer cells MDA-MB-231 on Matrigel collagen matrix can develop vasculogenic mimicry.(3)Brucine inhibited the development of vasculogenic mimicry of the MDA-MB-231 cells,in a dose-dependent manner.(4)Brucine also decreased the expressions of VEGF?VE-cadherin?Eph A2?MMP-2?MMP-9 in a dose-dependent manner.Conclusion: Brucine could inhibits the proliferation of MDA-MB-231 cells,and induce apoptosis,inhibits the development of vasculogenic mimicry by regulating the expression of VEGF?VE-cadherin?Eph A2?MMP-2?MMP-9.