Glioma is a common tumor originating in the brain that has a high mortality rate.Temozolomide(TMZ)is the first-line treatment for high-grade gliomas.However,a large pro-portion of gliomas are resistant to TMZ,posing a...Glioma is a common tumor originating in the brain that has a high mortality rate.Temozolomide(TMZ)is the first-line treatment for high-grade gliomas.However,a large pro-portion of gliomas are resistant to TMZ,posing a great challenge to their treatment.In the study,the specific functions and mechanism(s)by which cortistatin(CORT)regulates TMZ resis-tance and glioma progression were evaluated.The decreased expression of CoRT was detected in glioma tissues,and highly expressed CORT was associated with a better survival rate in pa-tients with glioma.CORT overexpression notably decreased the capacity of glioma cells to pro-liferate and migrate in vitro and to form tumors in vivo.CORT overexpression also markedly suppressed the viability and enhanced the apoptosis of TMZ-resistant U251 cells by regulating MGMT,p21,and Puma expression.Importantly,CORT overexpression reduced the resistance of gliomas to TMZ in vivo.CORT expression Was negatively correlated with MGMT expression in both glioma tissues and cells,and it was found that CORT inhibited NF-kB pathway activation in glioma cells,thereby inhibiting MGMT expression.In conclusion,CORT regulates glioma cell growth,migration,apoptosis,and TMZ resistance by weakening the activity of NF-kB/p65 and thereby regulating MGMT expression.The CORT/NF-kB/MGMT axis might be regarded as a molecular mechanism contributing to the resistance of glioma to TMZ.Our data also suggest that CORT regulates the viability and metastatic potential of glioma cells,independent of its effects on TMZ resistance,providing evidence of novel therapeutic targets for glioma that should be evaluated infurther studies.展开更多
基金supported by grants from the Department of Science and Technology of Sichuan Province,China(No.23ZDYF2212,23ZDYF2098)the Foundation for Sichuan Provincial People's Hospital(Sichuan,China)(No.2022QN06)Medico-Engineering Cooperation Funds from the University of Electronic Science and Technology of China(No.ZYGX2021YGLH209)and 2022 Tianfu Qingcheng Project,China.
文摘Glioma is a common tumor originating in the brain that has a high mortality rate.Temozolomide(TMZ)is the first-line treatment for high-grade gliomas.However,a large pro-portion of gliomas are resistant to TMZ,posing a great challenge to their treatment.In the study,the specific functions and mechanism(s)by which cortistatin(CORT)regulates TMZ resis-tance and glioma progression were evaluated.The decreased expression of CoRT was detected in glioma tissues,and highly expressed CORT was associated with a better survival rate in pa-tients with glioma.CORT overexpression notably decreased the capacity of glioma cells to pro-liferate and migrate in vitro and to form tumors in vivo.CORT overexpression also markedly suppressed the viability and enhanced the apoptosis of TMZ-resistant U251 cells by regulating MGMT,p21,and Puma expression.Importantly,CORT overexpression reduced the resistance of gliomas to TMZ in vivo.CORT expression Was negatively correlated with MGMT expression in both glioma tissues and cells,and it was found that CORT inhibited NF-kB pathway activation in glioma cells,thereby inhibiting MGMT expression.In conclusion,CORT regulates glioma cell growth,migration,apoptosis,and TMZ resistance by weakening the activity of NF-kB/p65 and thereby regulating MGMT expression.The CORT/NF-kB/MGMT axis might be regarded as a molecular mechanism contributing to the resistance of glioma to TMZ.Our data also suggest that CORT regulates the viability and metastatic potential of glioma cells,independent of its effects on TMZ resistance,providing evidence of novel therapeutic targets for glioma that should be evaluated infurther studies.
