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Inhibitory Effects Of Ligustrazine On Breast Cancer In Vivo And Study Of The Mechanism

Posted on:2011-06-02Degree:MasterType:Thesis
Country:ChinaCandidate:J MaFull Text:PDF
GTID:2154360305976049Subject:Department of General Surgery
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Breast cancer is one of the most common malignant tumors for women today. To discover possible the mechanisms of restraining the growth of tumor and its anti-angiogenesis of Ligustrazine by way of observing the expression of VEGF-A and VEGF-C on human breast cancer tissue on MDA-MB-231 nude mouse mode.MethodsExperimental MDA-MB-231 nude mice had been randomly divided into saline group, Ligustrazine in high dose group, Ligustrazine in low dose group, CTX group randomly after the subcutaneously implanted model bearing breast carcinoma cell line MDA-MB-231.The administrations began after the creation of nude mouse mode, which were as follows:the mice in saline group were given isotonic saline 0.2ml ip. once a day×3w; in CTX group were given CTX dilution(100mg.kg-1.w-1) 0.2ml ip. once a week×3w; in high dose group of Ligustrazine were given (200mg.kg-1.d-1)0.2ml ip. once a day×3w; in low dose group of Ligustrazine were given Ligustrazine (50mg.kg-1.d-1)0.2ml ip. once a day×3w,The experiment terminated on the 3th week. The mice were sacrificed after neck dislocation, observe the breast partial growth of transplanted tumor, tumor tissue taken, Immunohistochemical staining of CD34, counted MVD,quantitative observation of tumor angiogenesis, while detected VEGF-A and VEGF-C protein and mRNA of tumor tissues by immunohistochemistry and RT-PCRResults1,General state of nude mice After the administration,the nude mice all survived. The mice in CTX group were becoming depressed,drinking and eating less; other groups did not see this.2,Anatomical and pathological observation The cut surface was white, and was seen necrotic area in naked eyes; the pathology report demonstrated invasive ductal carcinoma.3,Tumor volume(V= Length×width2cm3/2)After the administration,the tumor volume in different groups(50mg/kg, 200mg/kg) of Ligustrazine was lower than in NS group(P<0.01).4,Tumor weight and tumor inhibitory rateAfter the administration,the tumor weight in different groups(50mg/kg, 200mg/kg) of Ligustrazine was lower than in NS group(P<0.01);the tumor inhibitory rate in high and low dose group of Ligustrazine were 36.5% and 35.3%.5,MVDAfter the administration,MVD in different groups(50mg/kg, 200mg/kg) of Ligustrazine was lower than in NS group(P<0.05); Compared with CTX group,there was no difference(P>0.05); the MVD inhibitory rate in high and low dose group of Ligustrazine were 31.6% and 29.6%.6,ImmunohistochemistryCompare with the NS group,the expression of VEGF-A and VEGF-C protein were decreased in different concentration (50mg/kg, 200mg/kg) of Ligustrazine by immunohistochemical study.7,RT-PCRCompare with the NS group,The ratio of optical density of VEGF-AmRNA and VEGF-CmRNA to that ofβ-actin were decreased in different concentration (50mg/kg, 200mg/kg) of Ligustrazine by PT-PCR(P<0.01),the reduction ratio of VEGF-A/β-actin in high and low dose group of Ligustrazine were 21.0% and 20.0%, the reduction ratio of VEGF-C/β-actin in high and low dose group of Ligustrazine were 21.7% and 19.9%.8,The relation between VEGF-A and VEGF-C in breast tumerThe expression of VEGF-A was postively correlated to the exprssion of VEGF-C in breast cancer (r=0.914,P<0.01) . Conclusion(1)Ligustrazine can decrease the growth of breast tumer, inhibition rate in high dose group and in low dose group is 37.1% and 34.9%.Compared with CTX , Ligustrazine may have some effect on improving life quality after the therapy. For example: diet, spirit and general healthy state.(2)Ligustrazine can inhibit the angiogenesis of breast tumer, inhibition rate of microvessel densit in high dose group and in low dose group is 31.6% and 29.6%.Compared with CTX , the difference is not statistically significant (P>0.05).(3)By the correlation analysis, VEGF-A and VEGF-C could have a synergistic effect in the occurrence and development of breast cancer.(4)Ligustrazine can restrain the growth and angiogenesis of breast cancer by inhibiting the expression of VEGF-A and VEGF-C proteins and mRNA in breast tissue...
Keywords/Search Tags:Ligustrazine, breast cancer, nude mice, MVD, VEGF
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