Inhibition of NF-κB results in anti-glioma activity and reduces temozolomide-induced chemoresistance by down-regulating MGMT gene expression

High levels of nuclear factor κB (NF-κB) activity in glioma specimens are associated with malignant grades and lower overall survival.

• Glioma specimens and cell lines exhibit constitutively high NF-κB activity.
• NF-κB expression correlates with malignant grades in glioblastoma multiforme (GBM) and inversely with overall survival.
• Inhibition of NF-κB leads to reduced glioma cell proliferation, S cell cycle arrest, and increased cell death.
• A significant correlation exists between NF-κB and O6-methylguanine-DNA methyltransferase (MGMT) expression in gliomas.
• Inhibiting NF-κB activity can down-regulate MGMT expression and restore sensitivity to temozolomide (TMZ) in vitro and in vivo.
• The combination of TMZ and NF-κB inhibitors, such as parthenolide, may enhance treatment effectiveness in chemoresistant gliomas.

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