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Research Of The Effect Of Pamd On Relative Gene Of Pancreatic Carcinoma

Posted on:2010-08-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y Q DuFull Text:PDF
GTID:1114360275487754Subject:Integrative basis
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Objective:To observe the anti-tumor effect of PAMD(phenolicalkaloids of Menispermum dauricum)on tumor-bearingmice,so that we can study the content of TNF-αin peripheral bloodof tumor-bearing mice to observe the effect of on expression ofgene and protein content of k-ras and DPC4 in tumour tissues oftumor-bearing mice and to observe the effect on apoptosis rate ofBXPC-3.Methods:The 40 metastatic tumor model of tumor-bearingmice were established with BXPC-3 cell line by hypodermic ofright oxter.After 24h the mice divided into 5 groups at random,andeach group has eight mice.PAMD high-dose group was treated with20mg/kg,mid-dose group was treated with 10mg/kg,low-dosegroup was treated with 5mg/kg,control group was given bycyclophosphamidum 156mg/kg,was model group given byisopyknic physiological saline and blank group given isopyknicphysiological saline but no tumor established.The effect onimmune organ index was detected and the tumor control rate andthe index of spleen was calculate.ELISA was carried out aftertreatment with PAMD to detect the cotent of TNF-αin peripheralblood.Meanwhile,the effect on extression of gene and protein ofk-ras and DPC4 in tumour tissues of tumor-bearing mice wasdetected by Real-time Fluorescence Quantitative PCR andWestern-blot.Flow cytometry was used to detect the apoptosis rateof BXPC-3 cells line.So that the inhibition rate of tumorproliferation were detected and the effect of express on relatedtarget gene was decided.We can investigate the target of PAMD tocancer of pancreas.Results:PAMD could inhibite the tumor growth oftumor-bearing mice of BXPC-3 cell line,The inhibition rates were 34.91%,52.83%,41.51%,respectively,which has the statisticalsignificance(P<0.01).Compared with the control group,the spleenindex of mid-dose group and low-dose grouphas statisticalsignificance(P>0.05),while,the PAMD high-dose group could notshowed markedly effect on immune organ index (P<0.05)Meanwhile,PAMD could decrease the content of TNF-αinperipheral blood of tumor-bearing mice,compared with the modelgroup with statistical significance (P<0.01)PAMD coulddown-regulate the expression of gene of K-ras mRNA in tumortissues and increase the DPC4 mRNA and its protein expression,compared with the model group with statistical significance(P<0.01)Meanwhile,PAMD could increase the apoptosis rate,showed markedly inhibiting action (P<0.01)Conclusions:PAMD could inhibite the tumor growth intumor-bearing mice of BXPC-3 cell line.The effect of inhibitionwas related by regulating immunologic function,transferringbiological activity of cytokine,inhibiting gene product of K-ras,protein of P21,over-expression of K-ras mRNA,hoisting theexpression of gene DPC4,influenting TGF-βaccess of signaltransmit,induceing apoptosis and split apart,so that it caninhibiting the growth of tumor.
Keywords/Search Tags:PAMD, K-ras, DPC4, BXPC-3, Antitumor effect
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