β-arrestin 1 Overexpression Increases Temozolomide Resistance in Human Malignant Glioma Cells

Many studies highlighted β-arrestins (β-arr) as essential proteins behind the regulation of major cell signaling pathways in different types of cancer. An impaired β-arrestin 1 (β-arr 1) activation/phosphorylation was suggested to be associated with a high malignant phenotype of glioma. Elevated levels of β-arrestin 2 (β-arr 2) mRNA were also found in advanced stages of breast cancer compared to early stages. In addition, β2-arrestin was also linked to a suppressive effect on tumor growth in other types of cancers such as prostate or non-small cell lung cancer. In this study, we analyzed the effect of β-arr 1 overexpression on the cytotoxic effect of Temozolomide (TMZ) in two malignant glioma (MG) cell lines: U-343MGa and Cl2:6. For this purpose, the cells were transected with β-arr 1 and then treated with different concentrations of TMZ for 24, 48 and 72 hours. At the end of the treatment, the cell viability was analyzed by Prestoblue viability assay. Our results showed that TMZ treatment induced cytotoxicity in MG cells while β-arr 1 transfection significantly reduced the TMZ cytotoxic effect in both U-343MGa and Cl2:6 MG cell lines. These results suggest that β-arr 1 overexpression may be a cause of TMZ resistance in MG.