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Proliferation And Migration Of The Bladder Tumor Cell Induced By The Inhibitor Of The Fibroblast Growth Factor Receptor And Its Possible Mechanism

Posted on:2013-04-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y HouFull Text:PDF
GTID:1264330401979161Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Part I T24proliferation and migration suppressed by FGFR inhibitor and MAPK pathwayAim:bladder cancer is very common in urinary tumor. It took almost3.2%of all mignignant tumors. And in bladder cancer, the transitional cell tumor was above95%which threaten the survival of the patients. Nowdays, although there were so many treatments for bladder cancer, still lower survival rate of5years. FGFR were almost in all urothelium. Some researches suggested that it could take a part in tumor formation. So the objective of this study was used to observe whether FGFR inhibitor could suppress T24proliferation and migration. This study could supply the clinic study data for the treatment of bladder cancer.Method:T24cells were treated with the final concentration of0、60、70、80μmol/L FGFR inhibitor (Sprouty) for12h,24h and72h. The inverted microscope was to see the cell number and the morphologic change. The sprouty treatment on the survival of the T24cells was supplied by MTT assay. The migration of sprouty on the T24was checked by Phagokinetic Track Motility. Western blot were used to explain the probable signal pathway of sprouty on the T24cells. Statistical Analysis:the values in the figures are expressed as the mean±standard deviation (SD). Statistical analysis of the data between the control and treated groups was performed by a Student’s t-test. Values of P<0.05were considered as significant.Result:Sprouty could inhibit the proliferation of T24. After treatment by sprouty, the T24cells were shrinkaged and apoptosis denpending on the concentration. The results of MTT also suggested that sprouty could suppress the survival of T24cell by time and contration dependment manner. Phagokinetic Track Motility results showed that sprouty could significantly inhibit the migration of T24cells. Further study of the signal pathway suggested that sprouty inhibit the phosphorylation of ERK and increase the JNK phosphorylation by western blot. But no effect was seen in P38.Conclusion:The proliferation and migration of T24could be inhibited by sprouty on MAPK pathway.Part II The tumor invasion of the formation and the mechanism of the bladder tumor were suppressed by FGFR inhibitorAim:Both infiltration and migration were determined by the turmor formation, development and cause the death of the patients. The migration of cancer cells was concluding the decreasing rate of adhersion, the adhersion between the cancer cell and basal membrane, degradation of the extracellular matrix and so on. In the first part, we had already explained the sprouty could inhibit T24cells proliferation and migration by MAPK. So in this part, the objective was to explore that whether sprouty could suppress the tumor formation and the mechanism of migration.Method:T24cells were injected subcutaneously on the fight flank of male BALB/c-nude mice. At a tumor size of approximately30mm3the mice were divided into four groups. Group A reveived no treatment, Group B were treated with bFGF. Group C were treated with sprouty and Group D were treated with both bFGF and sprouty, once daily for4weeks, respectively. After treatment, the mice were sacrificed the weight of the tumor. Also the tumors were extracted the total mRNA. The MMPs mRNA was to see by PCR.Result:The tumor growth in bFGF Group was significantly faster than the control group. And sprouty Group were suppressed on the formation of bladder tumor. Once treated with sprouty, the tumor formation induced by bFGF was slow. the mRNA of MMPs and cut down the regulation effect of bFGF could also be inhibited by sprouty.Conclusion:Sprouty which inhibit the bladder tumor formation could suppress migration of bladder cancer cells by regulating MMPs mRNA.
Keywords/Search Tags:bladder tumor, FGFR inhibitor, MAPK, T24cells, proliferation and migration
PDF Full Text Request
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