The sigma-1 receptor: potential role in the modulation of cellular radiation sensitivity

Direct interaction of the sigma-1 (σ1) receptor, an endoplasmic reticulum chaperone located in close vicinity to the mitochondrion, with a variety of proteins involved in essential processes regulating proliferation, survival, and death of cells, indicates a role of this protein in tumor biology. Since tumor therapies address precisely these processes to stop the growth of tumor cells, the σ1 receptor could be a suitable modulator of the effectiveness of selected therapies. Recent initial studies have shown not only antiproliferative effects of ligands targeting this protein, but also modulating effects in both chemotherapy and radiotherapy. However, in this regard the influence of functional expression of the σ1 receptor has not yet been fully clarified. The purpose of this pilot experiment was to investigate the role of σ1 receptor on cellular radiosensitivity in an in vitro model. Therefore, clonogenic assays were performed to assess the susceptibility of HEK293 cells, stably transfected with human σ1 receptor, towards irradiation (X-ray) in comparison to non-transfected cells. Moreover, irradiation combined with pharmacological treatment should prove whether agonistic and antagonistic ligand binding to σ1 receptor influences the effectiveness of radiation treatment. The data obtained are not fully conclusive by indicating, on the one hand, an involvement of σ1 receptor in radiation-induced effects along with pharmacological effects independent from the σ1 receptor level, on the other hand, suggesting limitations of the model used herein. Consequently, subsequent work will focus on the investigation of tumor cells with different receptor densities.