Overexpression of ILK promotes temozolomide resistance in glioma cells

Abstract

The present study aimed to investigate whether overexpression of integrin-linked kinase (ILK) affects drug resistance to temozolomide (TMZ) in glioma cells. To do this, a plasmid containing the ILK gene was transfected into the SHG-44 human glioma cell line, and cells were subsequently cultured in the absence or presence of TMZ. The expression levels of ILK, multidrug resistance-associated protein (MRP) and multi-drug resistance protein (MDR) were assessed in these cells. Cell growth and apoptosis were measured by MTT and Hoechst staining, and flow cytometry, respectively. In addition, the expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated x protein (Bax), and caspase-3 activity, were evaluated. The ILK-overexpressing SHG-44 cell was successfully constructed, and demonstrated increased expression levels of ILK, MDR and MRP compared with untransfected cells. Cell growth in the ILK+TMZ group was significantly greater, and the percentage of apoptotic cells in the ILK+TMZ group was significantly reduced, compared with the p enhanced green fluorescent protein (EGFP)-C1+ TMZ empty vector control group. Expression levels of the anti-apoptotic protein Bcl-2 were significantly increased and those of the pro-apoptotic protein Bax were significantly decreased (P<0.01) in the ILK+TMZ group compared with the pEGFP-C1+TMZ group. In addition, the activity of caspase-3 in ILK+TMZ group was significantly decreased compared with the pEGFP-C1+TMZ group (P<0.01). Overexpression of ILK therefore promoted the proliferation of SHG-44 human glioma cells, reduced apoptosis and reduced sensitivity to TMZ via decreasing the activity of caspase-3.