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 proportion 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 resistance 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 patients with glioma. CORT overexpression notably decreased the capacity of glioma cells to proliferate 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-κB 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-κB/p65 and thereby regulating MGMT expression. The CORT/NF-κB/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 in further studies.