Expression Of Akt, MTOR And STAT3 In Brain Gliomas And Their Significances

Background and ObjectiveThe human glioma is the highest incidence of central nervous system cancer, which accounts for about 50%-60% of adult primary intracranial tumors, including astrocytoma, ependymoma, oligodendroglioma, medulloblastoma, glioblastoma and so on. In the treatment of glioma there are several ways in which the three most effective treatment is surgery,radiation therapy and chemotherapy. Currently the main treatment is surgery. Because of glioma's invasive growth, the majority of tumors can not be completely removed and the necessity for more postoperative radiotherapy, chemotherapy and other adjuvant therapy. As the malignant biological behavior of gliomas, in which is especially glioblastoma with the highest degree of malignancy, strong proliferation and invasion, the recurrence rate is high, and the patient's prognosis is poor. Therefore, in-depth study of the pathogenesis of the glioma, could further enhance the understanding of the glioma and overall levels of treatment.Proliferation and apoptosis has always been the hot in the basis medicine study of the mechanism of tumor, and like other malignant tumors in the human body brain glioma cells also exist abnormal proliferation and apoptosis inhibition, which involve a variety of gene abnormalities expression or suppression. PI3K/Akt/mTOR signaling pathway controls many essential cell biological processes in tumor genesis and development, including apoptosis,transcription,translation,metabolism angiogenesis and cell cycle regulation. STAT3 is a member of the STAT family, which is involved in cell cycle and apoptosis regulation, involved in tumor angiogenesis,tumor cell invasion,metastasis and immune escape and other processes. With more and more in-depth understanding of mTOR pathway, a growing number of experiments confirmed that mTOR can regulate STAT3 protein expression and phosphorylation.This study was designed by detecting Akt, p-mTOR and p-STAT3 expression in brain gliomas, and a preliminary study of Akt, mTOR and STAT3 in glioma pathogenesis and its relationship to explore the relationship of the mTOR and STAT3 between the occurrence and development of glioma, in order to further clarify the mTOR and STAT3 protein expression and regulation, and provide a theoretical basis for prevention and treatment of glioma.Materials and MethodsSP immunohistochemical staining method and Western blot detection of Akt,mTOR and STAT3 expression in brain gliomas samples and normal brain tissue samples. Between the normal brain tissue and different groups of gliomas for comparison, use the Kruskal-Wallis'rank sum test and Spearman rank correlation as Statistical analysis. P<0.05 was considered as statistical significance.Results1. Immunohistochemistry showed that Akt protein was mainly distributed in the cytoplasm, the difference of expression of Akt between the high and low-grade gliomas and normal brain tissue shows statistically significant. Pairwise comparison shows that between groups of the high-and low-grade gliomas Akt expression difference was statistically significant, while low-grade gliomas and normal brain tissue are also differences between the expression level of statistical significance. Experimental results of Western blot and immunohistochemical results are consistent.2. Immunohistochemistry showed that p-mTOR expression mainly in the cytoplasm, the difference of expression of p-mTOR between the high-and low-grade gliomas and normal brain tissue shows statistically significant. Pairwise comparison shows that between groups of the high-and low-grade gliomas p-mTOR expression difference was statistically significant, while low-grade gliomas and normal brain tissue are also differences between the expression level of statistical significance. Experimental results of Western blot and immunohistochemical results are consistent.3. immunohistochemistry showed that most of p-STAT3 protein positive staining in the nucleus, the difference of expression of p-STAT3 between the high and low-grade gliomas and normal brain tissue shows statistically significance. Pairwise comparison shows that between groups of the high-and low-grade gliomas p-STAT3 expression difference was statistically significant, while low-grade gliomas and normal brain tissue are also differences between the expression level of statistical significance. Experimental results of Western blot and immunohistochemical results are consistent.4. In brain glioma tissue Akt and p-mTOR protein expression was positively correlated, and p-mTOR and STAT3 protein expression was positively correlated.Conclusions1. The expression of Akt,mTOR and STAT3 in human brain glioma increased.2. The increase expression of Akt,mTOR and STAT3 might be involved in the occurrence and development of glioma.3. with the increased level of malignant glioma, the expression of Akt,mTOR and STAT3 increased.4. Akt,mTOR and STAT3 in brain gliomas were in positive correlation, indicating that the three in brain gliomas have a certain link and the three may be able to become a target for glioma therapy, enhancing the clinical effect of chemotherapy.