Gelsolin is an actin-binding protein and acts as an important regulator of cell survival. This study aimed to determine the function of gelsolin in the radioresistance of non–small cell lung cancer cells. We examined the expression of gelsolin in radioresistant A549 and H460 cells and their parental cells. The effects of gelsolin overexpression and knockdown on the clonogenic survival and apoptosis of non–small cell lung cancer cells after irradiation were studied. The involvement of phosphoinositide 3-kinase/Akt signaling in the action of gelsolin was checked. We found that gelsolin was significantly upregulated in radioresistant A549 and H460 cells. Overexpression of gelsolin significantly ( P < .05) increased the number of colonies from irradiated A549 and H460 cells compared to transfection of empty vector. In contrast, knockdown of gelsolin significantly ( P < .05) suppressed colony formation after irradiation. Gelsolin-overexpressing cells displayed reduced apoptosis in response to irradiation, which was coupled with decreased levels of cleaved caspase-3 and poly adenosine diphosphate-ribose polymerase. Ectopic expression of gelsolin significantly ( P < .05) enhanced the phosphorylation of Akt compared to nontransfected cells. Pretreatment with the phosphoinositide 3-kinase inhibitor LY294002 (20 μmol/L) significantly decreased clonogenic survival and enhanced apoptosis in gelsolin-overexpressing A549 and H460 cells after irradiation. Taken together, gelsolin upregulation promotes radioresistance in non–small cell lung cancer cells, at least partially, through activation of phosphoinositide 3-kinase/Akt signaling.
Integrin β1-mediated acquired gefitinib resistance in non-small cell lung cancer cells occurs via the phosphoinositide 3-kinase-dependent pathway