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Experimental Study Of Promoter Methylation Of SFRP2in Colon Cancer Xenografts With125I Seed Implantation

Posted on:2014-02-22Degree:MasterType:Thesis
Country:ChinaCandidate:C X WangFull Text:PDF
GTID:2254330401963773Subject:Surgery
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Objective:To investigate tumor growth inhibition of colone oxenografts tumor and changes of methylation of SFRP2gene promoter in nude mice with125I seeds implantation. Evaluated the therapeutic effect of125I seeds on tumor and provided basic Anti-tumor mechanism of125I seeds bradytherapy in clinic.Methods:Experiment was divided into two parts。First The40nude mice bearing HCT-8colon cancer xenografts were randomly separated into4groups:.group A(implanted0.8mCi1251seeds,n=10)、group B(implanted0.4m Ci1251seeds,n=10)、group C (implanted OmCi1251seeds, n=10) and group D (control). Volume of tumor was measured every two days and tumor volume inhibition rate was calculated.Second,Nude mice were sacrificed on day22and take xenografts after1251seed implantation.The application of pyrosequencing was used to detected the level of SFRP2promoter methylation.Results:1.125I seeds can suppresses the growth of colon cancer xenografts in unde mice.The average xenografts volume in four group was (3.532±0.211),(3.467±0.185)、(2.446±0.102) and0.961±0.181) after125I seed implantation22days。Compared with control group, the significant inhibiting effect on xenografts volume was found early in group0.8mCi at fourth day (p=0.00) and in group0.4mCi at sixth day (p=0.01).Group0.8mCi had higher tumor inhibition rate (0.4101±0.158) then group0.4mCi(0.168±0.083)and significant difference was found between group (Z=-2.54, p=0.01).2.SFRP2gene promoter was highly methylation in D group,withe the average methylation index as0.870±0.006.The xenografts were treated withe different dose125I seeds (0.8mCi、0.4mCi、0mCi), the average methylation index of SFRP2promoter for each was0.578±0.057、0.685±0.394,0.867±0.023。Statistically difference was found among0.8mCi、0.4mCi and control groups (X2=47.413,p=0.000). The average methylation index of SFRP2in0.8mCi group was lowest,compared with control group (p=0.00) and group0.4mCi(p=0.02)Conclution:1.1251seed could suppresses xenograft growth。2.effect of inhibition had dose and time dependent at early stage of125I implantation.3.Hypomethylation of SFRP2gene promoter that125I seed inducted might be associated with inhibition of colon cancer xenografts.
Keywords/Search Tags:125I, colon cancer, SFRP2gene, methylation
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