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Specificity protein 1-modulated superoxide dismutase 2 enhances temozolomide resistance in glioblastoma, which is independent of O6-methylguanine-DNA methyltransferase
A protein that increases antioxidant enzyme levels may raise drug resistance in brain cancer, independent of a common DNA repair enzyme
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Abstract
Increased expression of the protein Sp1 is associated with reduced levels of reactive oxygen species in temozolomide-resistant glioblastoma cells.
- Temozolomide resistance in glioblastoma may occur independently of the DNA repair enzyme MGMT.
- TMZ-resistant glioblastoma variants show elevated Sp1 expression and decreased reactive oxygen species accumulation after treatment.
- The enzyme superoxide dismutase 2 (SOD2) is identified as a disease-related ROS scavenger that is co-expressed with Sp1 in resistant cells.
- Sp1 acts as a key activator of the SOD2 gene, enhancing its expression.
- Inhibition of Sp1 can reverse TMZ resistance and lower SOD2 levels in resistant glioblastoma cells.
- This inhibition strategy improved survival rates in an animal model of glioblastoma.
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