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The Establishment Of Leukemia Animal Model And The Contribution Of Icaritin To AML Or CML

Posted on:2014-05-28Degree:MasterType:Thesis
Country:ChinaCandidate:J WangFull Text:PDF
GTID:2254330401968887Subject:Pharmacology
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Leukemia is a malignant disease of hematopoietic system, which is classified to acutelymphoblastic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia,chronic myeloid leukemia and others, according to disease development and the originof leukemia cells. Chemotherapy is the main method used in the therapy of leukemia. Inrecent years, the research and development of various types of anti leukemia drugsbecome the hot topic. Stability of animal model of leukemia, good repeatability is veryimportant for the evaluation of drug screening.Through literature research, the methods of leukemia model mainly havesubcutaneous xenograft and peripheral blood. Leukemia model in subcutaneousxenograft is more easily established, and the technology is more mature. The changingtrend of tumor volume could be observed to accurately evaluating the efficacy ofanticancer drugs. For leukemia model in peripheral blood, the leukemia cells are injectedinto immunodeficient mice via tail vein, and grown in the blood or tissues. The life-spanof mice was the main index for evaluation. The progression of the model is close to thecharacters of leukemic patients, but many factors affect the stability of model. Thispaper focused on establishing the leukemia model in peripheral blood. The NOD/SCIDmice was irradiated by60Co γ ray, then inoculated K562cells or HL60cells to establishthe leukemia model of chronic myeloid leukemia or acute myeloid leukemia. Thesemodels were stable and repeatable.Icaritin is hydrolysis product of icariin in Epimedium. The results of cell experimentsindicated that the proliferation of MV-4-11cells and K562cell had been inhibited by icaritin. The IC50were5.95μ M,7.81μ M and36μ M,35.32. And icaritin couldsignificantly induced apoptosis of MV-4-11cells and K562cells, moreover, it couldmake MV-4-11cell G0/G1arrest. RT-PCR experimental results showed that icaritincould down-regulate STAT5gene expression, indicated that it was contributed to affectthe growth of MV-4-11cells.In vivo experiment, we established leukemia model in subcutaneous xenograft andperipheral blood, used for evaluating the anti-tumor activity of icaritin on acute myeloidleukemia and chronic myeloid leukemia. The experimental results showed that icaritincould inhibit the growth of MV-4-11cells in vivo, and prolong the life-span of leukemicmice inoculated with K562cells. The results indicated that icaritin had potentialanti-leukemia activity on AML and CML.
Keywords/Search Tags:Leukemia, chronic myeloid leukemia, acute myeloid leukemia, NOD/SCIDmice, animal model, K562cell, HL60cell, MV-4-11cell, Icaritin, STAT5
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