The nuclear transcription factor nuclear factor-κB inhibitor in glioma cells reversed the resistance of glioma cell lines to temozolomide

Abstract

Objective To reduce the expression of nuclear factor-κB (NF-κB) by inhibiting IκBα, and thereby reverse the temozolomide (TMZ) resistance of glioblastoma multiforme (GBM) cells, as well as to explore the relationship between NF-κB pathways and the expression of O6-methylguanine-DNA methytransferase (MGMT) in TMZ resistant cell lines. Methods We used U251 cells to build anti TMZ model TR-U251. Western blotting was used to detect the expression of NF-κB and MGMT in both cell lines, and we also observed changes in the level of resistance to TMZ by inhibiting the expression of NF-κB. Chi-square test of statistical methods was used for analysis. Results TR-U251 cell line model was successfully constructed. MGMT was highly expressed in TR-U251 cells, but was almost undetectable or very low in parental U251 cells. Likewise, phosphorylated p65 showed the same expression tendency. Compared with the parental U251 cell line, the expression of the sub-structure p65 of NF-κB in TR-U251 cells was 5.4 times higher that of the parental cells. When exposed to 80 μmol/L TMZ for 24 to 96 h, the survival rate of TR-U251 cells decreased slowly from (97.6±1.4)% to (78.3±3.6)%, while exposure to 50 μmol/L of bay11-7082, the survival rate decreased from (97.9±4.4)% to (64.2±2.3)%. However, the survival rate of cells exposed to 80 μmol/L TMZ combined with 50 μmol/L bay11-7082 decreased from (91.6±1.9)% to (27.8±5.7)% (P=0.004). The combination of TMZ and BAY11-7082 treatment significantly decreased the survival of cells as compared with TMZ alone or BAY11-7082 TMZ alone. Conclusion NF-κB activation has obvious relevance with the expression of MGMT degree in glioma. NF-κB and MGMT involved in the regulation of TMZ resistance of glioma cell lines. Inhibition of NF-κB decreased the activity of MGMT. Key words: Glioma; Nuclear factor-κ B; O6-methylguanine-DNA methytransferase; Temozolomide; Tolerance