| Objective:Malignant tumor is one of important reasons that threaten mankind health and result in dead . however, drug fast is crucial problem in the process of tumor therapy. drug resistance is that tumour cell is insensitivity to chemotherapeutics, drug resistance include natural exist (primary drug-resistance) and induced by primary drug-resistance (acquired drug-resistance). multidrug resistance is one of important patterns , characteristic of it is that once cell happened drug fast to certain medicine ,meanwhile generated cross tolerance to others medicine with different structure and mechanism of action . multidrug resistance gene include in MDR1,MRP,GST-Ï€,MGMT and so on, there are manydrug resistance gene express in tumor drug fast cell illustrated that drug fast factor possess multiplicity and complexity, furthermore, different drug resistance gene may exist synergistic effect . Human erythroleukemia cell K562 and human erythroleukemia drug fast cellK562/ADM induced by Adriamycin aapproachcted as study and research object in this experiment .Approach to multidrug resistance related gene change in human erythroleukemia drug fast cell K562/ADM treated by Adriamycin and preliminary research mechanism .Method:Cell culture ; The viability of cells was measured by MTT assay; Observe K562 and K562/ADM cell morphology change in the administration process ; Detect mRNA levels ofMDR1,MRP,MGMT,GST-Ï€by RT-PCR .Result:1. MTT showed that mitomycin can decease survival rate of K562 cells in a dosage dependent mode after 48 hours , but survival rate of K562/ADM cells were not change obviously . meantime . survival rate of K562/ADM cells great higher than that of K562 cells in cell treated by same dose .2. morphology change of K562 cells and K562/ADM cells were great difference in cells treated by mitomycin ,K562 cells dead became more and more with the dose increasing , but change of K562/ADM cells were not different .3. RT-PCR results showed ,compared with K562 cells ,mRNA expression of MRP,MDR1,MGMT increased in the K562/ADM cells , but mRNA expression of GST-Ï€is higher and not difference beween K562 cells and K562/ADM cells .Discussion:At present , people have known that there are many correlated action mechanism about leukemia drug fast , MDR,MRP,MGMT,GST-Ï€were selected and acted as detect objective this text , emphasize on approaching change of MDR,MRP,MGMT and GST-Ï€in leukemic drug fast cell , and reseaching relation beween various kinds drug resistance gene and cell drug resistance .Leukemic cell counteracted chemotherapeutics and produced multidrug resistance that is critical in acute leukemia curative effect , research investigated , tumor multidrug resistance mechanism is multiplicity ,and result by multiple factor and multiple gene unification , moreover , various kinds drug resistance gene action mode and action site are different . multidrug resistance gene include in MDR1,MRP,GST-Ï€,MGMT and so on . There are manydrug resistance gene express in tumor drug fast cell illustrated that drug fast factor possess multiplicity and complexity, furthermore, different drug resistance gene may exist synergistic effect . P-gp and MRPof multidrug resistance gene MDR1 Protern products are overflow pump that dependented on enegy and located on cellular membrane , MDR1 express highly can pump cytotoxic drug that after entered cell out and result in multidrug resistance . Study showed that MDR1 overexpression in leukemia cells is one of important drug fast mechanism . MRP drug fast mechanism is that made medicine in the cells expulsion , lower medicine density in thecells . MRP can identify and transport substrate that conjugate with GSH , called GSH- X pumb . GST-Ï€can catalyze binding of GSH and alkylating agent and reduce toxicity . otherwise , GST-Ï€that possess peroxydase activity can lower toxic effect of lipid peroxidation Hydroperoxide and free radiclecytotoxic generate by toxic drug such as Adriamycin .RT-PCR results showed that K562 cells is scarcely express MDR1 , MRP mRNA , compared with K562 cells , MDR1 and MRP mRNA is overexpression in the K562/ADM cells , expression of MGMT mRNA increasing but GST-Ï€change is not very different . all of that high indicated . MGMT and MRP mRNA expression increased , but MDR1 expression decreased of the K562/ADM cell treated with Mitomycin MRP is one of causes that drug resistance of K562/ADM , MDR1 and MGMT can have relation with drug resistance in here , GST-Ï€have little relation with this mechanism .We used cell line that can resist Adriamycin , up to now , study thought that Adriamycin repressed tumor thought interfereing with transcription and preventting DNA synthesis . Mitomycin can repress DNA reproduce and make DNA collapse . this experimental results showed cell survival rate were not influence in the K562/ADM cells , but cell survival rate of K562/ADM cells were descend , this showed K562/ADM cells is drug fast not only to Adriamycin but also to mitomycin .Conclusion:1. Mitomycin can result in human erythroleukemia K562 cells injury , but can not influce obviously on human erythroleukemia K562/ADM cells that induced by Adriamycin .2. K562/ADM cells is drug resistant not only to Adriamycin but also to mitomycin .3. MRP is one of causes that drug resistance of K562/ADM , MDR1 and MGMT can have relation with drug resistance in here .4. GST-Ï€have little relation with mechanism of mitomycin drug fast .In a word, mitomycin can result in human erythroleukemia K562 cells injure , but can not influce obviously on human erythroleukemia K562/ADM cells that induced by Adriamycin. K562/ADM cells is drug fast not only to Adriamycin but also to mitomycin . MRP is one important case of the drug resistance of K562/ADM , MDR1 and MGMT can have relation with drug resistance here. GST-Ï€have little relation with mechanism of mitomycin drug fast .
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