Effect of Radiation on self-renewality of prostate cancer stem cells.

Abstract

Introduction: CSCs have been identified in prostate cancer (PCa), one of the most diagnosed malignancies in men over the world, for which radiation resistance is a major problem in the treatment of advanced stages. Cancer stem cells (CSCs) have the ability to self-renew and differentiate to give rise to heterogeneous phenotype of the tumor cells. It is believed that CSCs are involved in metastasis, recurrence and therapy resistance in various cancers. Recently CSCs have been identified in prostate cancer. In vitro one of the main properties used to enriched cancer stem cells is their capacity to form spheres in non-adherent culture conditions. Materials and Methods: Human prostate carcinoma cell line (DU145) were plated in serum-free suspension culture system allowed for tumorsphere forming that enriched cancer stem cells. To identify prostate CSCs in adherent cells and nonadherent sphere cells of prostate cancer cell lines, the expression of the CD133 and CD44 cell-surface markers were assessed by flowcytometry. To evaluate of different doses of radiation (electron 6 MeV) on the self-renewal and proliferation of the Du145, sphere-formation assay (SFA) and plating efficiency (colony formation assay (CFA)) were assessed. The results were comparing with the parental cells. SFA is based on the self-renewing properties unique to CSCs. CFA is used as a measure of the proliferative potential of cells. Results: The results show that both SF (CFA) and SF (SFA) declined with the increase of radiation dose in cells treated as monolayer or sphere culture. However, the extent of reduction in cells treated as monolayer culture was significantly higher compared to cells treated as spheroids, suggesting higher resistance of spheroids to radiation. According to these results, tumorspheres from PCa showed more radioresistant than bulk of tumor. Conclusion: Due to the relative resistance of CSCs to radiotherapy, determination and characterization of radioresistance of CSCs in the prostate tumor is the key to develop more efficient therapeutic strategies.