Study Of The Difference Of Expression Of MGMT And Drug Resistance-related Proteins In Primary And Recurrent Gliomas

Background:Glioma is the most common primary malignant tumor occurred in the intracranial.Due to its highly aggressive behavior,it’s extremely difficult to achieve total excision.Morality and the rates of recurrence of the patients hover highly even the patients got postoperative radiotherapy and chemotherapy.Therefore,we need to explore the reason for the high rates of recurrence and explore the new medicine or the therapies against that.Recent researches showed that drug resistance-related proteins play an important role in the drug resistance of the primary and recrudescent glioma and impact the prognosis of the patients in varying degrees.Therefore,downregulating the levels of the drug resistance-related proteins in glioma cells is an important way to enhance the sensibility of the chemotherapy against glioma and improve the prognosis of the patients.Silibinin,which serves as a kind of routine liver-protect drug widely used in clinical,is the main active constituent of silymarin.In recent years researches showed that silibinin could exert the anti-tumor effect against kinds of malignant tumors by different mechanisms.However,the effect of the silibinin acting on the drug resistance-related proteins in glioma cells requires further researches.Objective:Select new and recrudescent glioma in different pathological grades randomly and compare the difference of the expression of MGMT and drug resistance-related proteins in these patients’ tumors.And the U87 cells were established to investigate the silibinin’s anti-glioma effects and the effects of drug resistance of glioma.Methods:1.Collect glioma specimens of 8 patients in different pathological grades randomly.And western blotting was used to test the difference in the expression of the drug resistance-related proteins including MRP1,P-GP and MGMT,NF-κB in these patients.2.Collect new glioma specimens of 4 patients and recurrent glioma specimens of 4patients in different pathological grades randomly.And western blotting was used to test the difference in the expression of the drug resistance-related proteins including MRP1,P-GP and MGMT,NF-κB in these patients.3.U87 and U87 TR cells were cultured in vitro and western blotting was used to detect the levels of the drug resistance-related proteins including MRP1,P-GP and MGMT,NF-κB in these samples.And western blotting was used to detect the levels of these drug resistance-related proteins in the samples affected by silibinin after a certain time.4.Western blotting was used to detect the levels of the drug resistance-related proteins including MRP1,P-GP and MGMT,NF-κB in the samples of silibinin of different concentrations.5.LDH release assay was used to detect the cell death ratio of U87 cells affected by temozolomide and silibinin.Results:1.The levels of the MRP1,P-GP and MGMT,NF-κB increased as the pathological grades increased in the glioma specimens of 8 patients selected randomly.2.In the patients selected randomly,the levels of MRP1,P-GP and MGMT,NF-κB in the recurrent glioma specimens were significantly higher than new glioma specimens at the same grades.3.The levels of MRP1,P-GP and MGMT,NF-κB of the U87 TR cells cultured in vitro were higher than U87 cells significantly.The levels of these drug resistance-related proteins decreased as time went by in the U87 and U87 TR cells affected by silibinin.4.The levels of MRP1,P-GP and MGMT,NF-κB decreased as the concentration of the silibinin increased in the U87 and U87 TR cells affected by silibinin.5.Cell death can be shown in the samples of U87 cells affected by the silibinin and temozolomide respectively,and the cell death ratio increased after the U87 cells were affected by the combination of silibinin and temozolomide.Conclusion:1.The drug resistance increases as the pathological grades of glioma increased.2.Most of the glioma’s drug resistance increases after the recurrence.3.Silibinin can reduce the drug resistance of glioma.4.The injury effect to glioma cells is stronger by the combination of silibinin and temozolomide than the use of the two drugs respectively.