关键词: 马钱子碱, 乳腺癌, 细胞凋亡, 血管生成拟态

Abstract: Background and purpose: The existence of vasculogenic mimicry (VM) in a large variety of highly invasive tumors, such as breast cancer, may lead to less effective traditional anti-angiotherapy. Brucine, a natural plant alkaloid, isolated from the seeds of medicinal herb, Strychnos nux-vomica Linn, has the potential antiangiogenic effect. This study aimed to explore the effect of brucine on vasculogenic mimicry formation of breast cancer cell lines MDA-MB-231 in vitro and the potential mechanisms. Methods: The inhibitory effect of brucine on growth of MDAMB-231 cells was measured by MTT method. Annexin Ⅴ-FITC/PI binding assay was used to measure the apoptosis rate of MDA-MB-231 cell after treatment with different concentrations of brucine. Hoechst 33342/propidium iodide (HO/ PI) dual staining was used to assay cell death detection. A three-dimensional system of breast cancer cell lines MDAMB- 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 protein level of the related marker molecules (VEGF, VE-cadherin, EphA2, MMP-2 and MMP-9) of VM were determined by Western blot. Results: 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. Brucine inhibited the development of vasculogenic mimicry by the MDA-MB-231 cells. Brucine also decreased VEGF, VEcadherin, EphA2, MMP-2 and MMP-9 in a dose-dependent manner. Conclusion: Brucine could inhibit the proliferation of MDA-MB-231 cell and induce apoptosis. It inhibits the development of vasculogenic mimicry by regulating the expression of VEGF, VE-cadherin, EphA2, MMP-2 and MMP-9.

Key words: Brucine, Breast cancer, Cell apoptosis, Vasculogenic mimicry