Overexpression Of MiR-874 Potentiates Chemosensitivity Of Glioblastoma To TMZ

Glioblastoma is one of the most common intracranial primary vicious tumors of the brain.At present,the main effective treatment for glioblastoma is surgery plus radiotherapy,chemotherapy and other comprehensive treatment.Glioblastoma is invasive growth,the operation is difficult to completely remove,easy to relapse after surgery,and chemotherapy and radiotherapy are often resistant,so the prognosis is very poor,the average survival time of patients is generally not more than two years.TMZ is a DNA alkylating agent that causes inactivation of O6-methyltransferase-DNA.O6-methylation in the next DNA replication cycle can not match the correct base pair,the formation of DNA strand gap,and ultimately lead to cell apoptosis.Studies have shown that temozolomide can significantly improve the prognosis of patients with glioma,glioma has become a first-line chemotherapy drugs.However,due to the presence of glioma in the brain,drugs need to penetrate the blood-brain barrier,as well as anti-cancer drugs and other adverse factors,the treatment and prognosis of glioma is not ideal.Therefore,it is urgent to explore the pathogenesis of glioma and find a new method to enhance the sensitivity of tumor chemotherapy.The expression of miR-874 transfected miR-874 mimics up-regulated in glioma cells,given temozolomide in the treatment of 24,48 hours later,according to the results of MTT,we found that compared with the control group,miR-874 combined with TMZ treatment can significantly inhibit U87 and LN229 glioma cell proliferation activity,the difference is statistically significant;V/PI and mitochondrial membrane potential of Annexin flow cytometry analysis showed that,compared with the other three groups,apoptosis of glioma cells in the treatment group of miR-874 combined with TMZ was the most obvious,significant difference was statistically significant(P < 0.05);Through the Transwell experiment,we found that miR-874 combined with TMZ group,the migration of glioma cell invasion ability was inhibited,the difference is statistically significant;Western Blotting results showed that the p-STAT3/STAT3 signal pathway of miR-874 combined with TMZ group was inhibited,anti apoptosis protein Bcl-2 expression decreased apoptosis protein Bax expression levels.,the expression level of migration and invasion related MMP-2?MMP-9 protein decreased,the difference was statistically significant.MTT results showed that compared with the control group,miR-874 combined with TMZ treatment can significantly inhibit U87 and LN229 glioma cell proliferation activity,the difference is statistically significant;V/PI and mitochondrial membrane potential of Annexin flow cytometry analysis showed that the relative three groups,glioma cell apoptosis in the treatment group of mi R-874 combined with TMZ was the most obvious,significant difference was statistically significant(P < 0.05);Transwell test showed that miR-874 combined with TMZ group,the migration of glioma cell invasion ability was significantly inhibited,the difference was statistically significant(P < 0.05);Western Blotting,p-STAT3/STAT3 miR-874 and TMZ signaling pathway the group was inhibited,Bcl-2 expression decreased,Bax expression level increased,the expression level of MMP-9?MMP-2 are decreased,the difference Statistically significant(P < 0.05).MTT found that miR-874 transfection can significantly enhance the TMZ activity to inhibit the growth of glioma cells and mitochondrial membrane potential;V/PI Annexin flow cytometry analysis showed that miR-874 combined with TMZ therapy can significantly enhance temozolomide on apoptosis of malignant glioma cells induced by the mechanism may be associated with the p-STAT3/STAT3 signaling pathway was inhibited,Bcl-2 expression decreased expression of Bax,MMP-2,MMP-9,Transwell showed low expression;transfection of mi R-874 can significantly inhibit the migration and invasion of glioma cells.These results suggest that miR-874 overexpression in malignant glioma cells can enhance the sensitivity of glioma cells to TMZ by regulating the p-STAT3/STAT3 pathway,and they have synergistic effects in the treatment of malignant glioma.To clarify the role and mechanism of miR-874 in the treatment of glioma cells is helpful to the further understanding of the drug resistance of malignant tumors.