| Objective: Gliomas account for 80% of central nervous system malignancies,and the incidence is high,which is extremely difficult to cure.Although with the development of modern medicine,radiotherapy,chemotherapy,targeted therapy and other treatment programs have been written into the guidelines and gradually applied to the clinic,but its therapeutic effect has not yet made a significant breakthrough.However,the role of endoplasmic reticulum stress apoptosis in tumors has attracted great attention in the research community.Among them,the neuronal polar molecule glycogen synthase kinase-3?(GSK-3?)endoplasmic reticulum The mechanism of stress apoptotic pathway in tumors is a hotspot in recent years.However,the research on GSK-3? endoplasmic reticulum stress apoptotic pathway in different grades of glioma is extremely rare at home and abroad.In this study,the expression trends of GSK-3? endoplasmic reticulum stress-related apoptosis pathway-related proteins in normal brain tissue and different grades of glioma tissues were determined,and the GSK-3? endoplasmic reticulum apoptosis pathway was explored at different levels of glia.The difference in tumor expression and its significance provide a strong basis for the precise treatment of glioma.Methods:A total of 35 hospitalized patients from our Department of Neurosurgery from December 2017 to December 2018 were enrolled in different grades of glioma and normal controls.Tumor tissues were classified according to medical pathology.The WHOI-WHOII assessment is classified as a low level and the WHOIII-WHOIV level is classified as a high level.Includes 14 low-grade glioma groups and 16 high-grade glioma groups.The other five normal brain tissues were derived from brain trauma or cerebral hemorrhage.The other five normal brain tissues are from the normal brain tissue of the non-functional area.Each brain tissue specimen was stored in a part of the wax block for subsequent TUNEL method(chromogenic method)to measure its apoptotic index(AI);the other part was stored in liquid nitrogen for Western blotting to detect GRP78,The expression trends of IRE1,ATF6,PERK,p-Tyr216-GSK-3?,p-Ser9-GSK-3? and caspase3 were analyzed,and the significance was analyzed.Results:The AI values of different grades of gliomas detected by TUNEL showed that the AI values of normal control group,low-grade glioma group and high-grade glioma group were 8.212±0.321,69.635± 1.433,21.711±0.325,respectively.The AI value of the glioma group was higher than that of the normal control group(P<0.05),while the AI value of the glioma group was negatively correlated with the degree of malignancy(r=-0.725,P=0.000).Western blot analysis showed that compared with the normal control group,the expression of GRP78 was increased,and the expression of IRE1,ATF6 and PERK was decreased(P<0.05).The expression of the key protein p-Ser9-GSK-3? was increased but the expression of p-Tyr216-GSK-3? was decreased(P<0.05),and the expression of caspase3 was increased(P<0.05).With the increase of tumor grade,the expression of GRP78,IRE1,ATF6 and PERK in glioma group increased(P<0.05);the expression of p-Ser9-GSK-3? was down-regulated but the expression of p-Tyr216-GSK-3? was increased(P<0.05);The expression of caspase3 was decreased(P<0.05).Conclusions:1.The AI value of low-grade glioma is higher than that of high-grade glioma,indicating that the progression of glioma may inhibit cell apoptosis.2.The increase of apoptotic index in glioma group and the expression of GSK-3? endoplasmic reticulum stress cell apoptosis pathway-related protein indicate that GSK-3? endoplasmic reticulum stress cell apoptosis pathway is initiated in glioma and carried out.3.In low-grade glioma cells,there may be a mechanism of inhibiting the expression of IRE1,ATF6,PERK and p-Tyr216-GSK-3?,thereby promoting apoptosis.With the progress of glioma,the expression of IRE1,ATF6,PERK,GRP78 and p-Tyr216-GSK-3? increased gradually,and the expression of P-Ser9-GSK-3? and caspase3 decreased gradually.These results suggest that GRP78,IRE1,ATF6,PERK and p-Tyr216-GSK-3? may be involved in the progression of glioma;glioma cells may be inhibited by inhibiting P-Ser9-GSK-3? and apoptosis.The expression of protein caspase3 further inhibits the apoptosis of glioma cells and promotes the progression of glioma.4.Inhibition of IRE1,ATF6,PERK in glioma cells by promoting the expression of p-Ser9-GSK-3? and apoptosis-executing protein Caspase3 in glioma GSK-3? endoplasmic reticulum stress.The expression of GRP78 and p-Tyr216-GSK-3? may be of great significance in inhibiting the progression of glioma,which provides a strong basis for guiding the accurate treatment of clinical glioma. |
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