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Study On New Drug Exploitation Of Reversing Tumor MDR

Posted on:2006-01-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:T X WangFull Text:PDF
GTID:1104360155453705Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Malignant tumor is one of the most disease which menance people's life and health , its incidence and death rate have an increasing trend . So how to cure cancer effectively is an important task we faced . At present , the therapy of malignant tumor has come into a comprehensive age . Along with the development of all kinds of new drugs and basic investigations , chemotherapy has more and more important role in comprehensive therapy of cancer . But , after many cancer patients come through effective chemotherapy initially , they recrudesce again . An important cause leading to chemotherapy failure is emergency of multidrug resistance (MDR) . So-called MDR is defined as tumor cells resist to not only previously used cytostatic agents , but also cross-resist to other drugs having different structure and function . Though combination chemotherapy make a number of malignant tumors such as acute leukemia patients acquire remission and extend survival time , 15%-30% of patients have primary drug resistance , 60%-80% of patients develop secondary drug resistance . It is estimated that the cause of death of approximately 95% malignant tumor patients relate to MDR . Therefore , MDR is a major obstacle in the treatment of malignant tumors . How to successfully reverse MDR is a study hot spot and an impending problem in tumor-treatment fields .In theory , overcoming MDR mostly has two approaches . One is empoldering new anticancer agents , other is searching drugs of reversing multidrug resistance , when they are combined with anticancer agents ,theymake sensitivity of MDR tumor cells on anticancer agents resumed .There are not reversal agents that are successfully used in clinic by far. So searching new MDR reversal agents of high effect , low toxin is exigent and essential. So we develop such study as follow:Experiment One Study on Reversal Effect of GLM Chloroform Distill Substance-MYJ1 on MDR Tumor Cells[Aim] To know whether Chinese GLM can reverse tumor cells MDR. [Methods]1. MTT assay , trypanblue dyeing assay determine cytotoxity of MYJ1.2. Accummulation and exclusivation experiment of Rhodamine determine the function of P-glyciprotein( P-gp) on membrane of tumor cells.3. RT-PCR assay determine the expression of MDR 1 gene in MDR tumor cells.[Results]1. There are not distinct differentiation between sensitive cell and resistant cell when MYJ1 was used only.2. Inhibitor rate of ADM on MDR tumor cells was distinct increased after MYJ1 was combined with ADM . Reversal multiple of MYJ1 on K562/ADM cells is 6.28 , and that of it on MCF-7/ADM cells is 5.78 .3. Rhodamine (Rh123) accumulation and exclusivation experement showed that after MYJ1 was used , intracellular Rh123 concentration was increased and along with MYJ1 concentration increasing , intracellular Rh123 concentration also increase .4. MYJ1 can not inhibitor the expression of MDR1 of multidrug resistant cells.[Conclusion] Chinese GLM can reverse MDR of tumor cells.
Keywords/Search Tags:multidrug resistance, reverse, tumor cells, Chinese drug
PDF Full Text Request
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