| Objective:Diallyl Trisulfide is one of the main active component of garlic, a large number of studies have shown that the organic sulfur compounds of garlic has the effect of prevention and treatment of cancer, and the number of sulfur atoms was relevant. The anti-tumor researchs of garlic mainly tend to prevent activation of carcinogens, inducing apoptosis, blocking the cell cycle, etc., but the effect of inhibit tumor metastasis is relatively limited. Given the current studies on diallyl sulfide inhibit human breast cancer cell malignant behavior during hematogenous metastasis have not been reported, we choose highly invasive human breast cancer cell line MDA-MB-231 to investigate the effect of DATS on malignant biological behavior during hematogenous metastasis and explore its mechanism.The aim of this study was to provide experimental evidence for clinical development of low toxicity and high efficiency antitumor drugs.Methods:The experimental study was divided into two parts. Part one was about the effect of DATS on malignant behavior of MDA-MB-231 breast cancer cell during invasion and hematogenous.And part one is divided into two chapter.In first chapter, the establishment of the tumor-matrix adhesion model, tumor mobility and migration model, tumor invasion model was to study the effect of DATS on breast cancer malignant behavior during the process of invasion and degradation basement membrane.In chapter two, the research was about the effect of DATS on tumor-platelet interaction. Through the establishment of the tumor-platelet adhesion model, actived-platelets induced tumor mobility and migration model, the study was to investigate effect of DATS during tumor cell hematogenous metastasis, we also studyed the effect of DATS on platelet activation and aggregation.The second part was to the study the molecular mechanisms of DATS during breast cancer invasion and hematogenous metastasis. This part by the use of Real-time PCR, RT-PCR technology, Western Blotting and ELISA technology on breast cancer cells, we studyed the effect of DATS on mRNA level and protein level Expression of matrix metalloproteinase (MMP2, MMP9) and their inhibitors TIMP1, Integrins(β1,β3).Conclusion:DATS could inhibit breast cancer mobility,migration and invasion basement membrane,but have no effect on adhesion between breast cancer and membrane; DATS could also inhibit the activation and aggregation of platelets, the adhesion between breast cancer cell and platelets, breast cancer cell mobility and migration induced by actived platelets. The anti-metastasis effect of DATS was due to the inhibit effect of mRNA expression and protein expression of Integrin (3, MMP2,MMP9, DATS could also promote the expression of TIMP1. All these datas suggested DATS inhibit breast cancer cell invasion and hematogenous metastasis potentially. This research provided referenced value on anti-tumor metastasis of garlic, so that we can make further development and utilization. |