Inhibition Effect Of Low Molecular Weight Heparin On The Growth And Metastasis Of Human Mammary Carcinoma Cell Implanted In Nude Mice

Background and Objective: Angiogenesis is a complex, multi-stepprocess that results in the formation of new blood vessels from pre-existingvascular nets. In normal tissues, the stimulative factors of vasculogenesisand the inhibitory factors of vasculogenesis are in the state of equilibrium,whereas in tumor tissues, this equilibrium is broken and the activities of thestimulative factors are enhanced.It induces and promotes the formation ofnew blood vessels and provides an essential condition for the subsequentdevelopment and metastasis of the tumor. In this complex process, VEGF(vascular endothelial growth factor) is currently considered to be a moreconfirmable stimulator than other factors and plays a critical role in theprocess of angiogenesis in tumor.It can distinctly accelerate the mitogenesis,proliferation and migration of the endothelial cells,and can promote thevascular permeability and the formation of new blood vessels.As a measurable index, MVD(microvessel density) is now graduallyaccepted as a major standard in evaluating the activities of the new bloodvessels.Angiogenesis plays a very important role in the process ofcarcinogenesis,growth,invasion and metastasis in BC(breast cancer),which isa kind of entity tumor. Many researches showed that VEGF was highlyrelated to the angiogenesis of BC.The increase of VEGF and MVD maypromote lymph node metastasis and relapse of BC.VEGF and MVD mayhave prognostic value in RFS(relapse-free-survival) of BC patients.As a traditional anticoagulant, LMWH(low molecular weight heparin)can also interfere the development of tumor by changing the environment ofthe tumor cells, and have a certain value in the treatment of tumor. Thesignificant inhibition effect of LMWH in liver cancer in animal experimentshad already been reported. But the inhibition effect of LMWH in BC in livebody has not been reported yet. The change of the expressions of VEGF andMVD in tumor samples of different treatement groups including LMWH andother control groups will be detected by immunohistochemical and WesternBlot, RT-PCR technique respectively. The inhibition effect of LMWH inangiogenesis,growth and metastasis of BC will be discussed, and it is expected to provide a experimental foundation for the further application ofLMWH in clinical therapy of BC.Methods 50 nude mice were successfully built up as BC models byimplanting human MCF-7 cells.Animals were randomly divided into 5groups: chemotherapy group,LMWH group,semi-dose LMWH group, endo-crine group and NS(normal saline)group. During 4 weeks of treatment,thegeneral condition of the nude mice and the development of the tumors wereobserved. After 28 days,the model mice were sacrificed by taking off thecervical vertebra and the expression of VEGF and MVD in the tumorsamples were dectected by immunohistochemical and Western Blot methods,RT-PCR technique respectively.The difference of the expressions of VEGFand MVD in each group and the correlation between the expressions ofVEGF and MVD were analyzed respectively.Results After 4 weeks of treatment,the expressions of VEGF and MVDin AC group, LMWH group, semi-dose LMWH group and TAM group weresignificantly lower than that in NS group(P＜0.01). Among all thesegroups,the expressions of VEGF and MVD in LMWH group decreasedmarkedly,but there is no statistical significance between these groups.Conclusions 1, LMWH can inhibit the expressions of VEGF and MVDat the levels of mRNA and proteinum in the MCF-7 nude mice models.2,LMWH can inhibit the growth and metastasis of BC in the MCF-7 nudemice models. 3, There is no statistical significance between the inhibition ofLMWH group and the inhibition of chemotherapy, endocrine therapy groupor semi-dose LMWH group.