Abstract 3452: The role of CX3CR1 in resistance of ovarian carcinoma cells to radiation therapy

Abstract

Abstract Ovarian carcinoma is a leading cause of death from gynecologic malignancies. The current standard of care, a combination of chemotherapy and radiation, fails to keep patients in remission. Thus, modifications of the therapy and the combinations with the new molecular biological technologies are crucial for the development of the modernized approaches to combat this disease. Previous attempts to use radiotherapy as an additional treatment was not successful mainly due to the dose-related side effects, as well as radioresistance. Therefore, mechanistical understanding of the biology of ovarian carcinoma could offer ways to overcome current problems. Fractalkine receptor (CX3CR1) belongs to a chemokine family of G protein-coupled receptors, the most frequently and successfully drug-targeted group of proteins. Interaction of chemokines with their receptors plays a pivotal role in homing distant metastasis, as well as promoting migration, adhesion, and proliferation in many types of cancer. This project is aimed at understanding the role of CX3CR1 in sensitization of epithelial ovarian cancer cells to radiotherapy. Our data indicate that downregulation of CX3CR1 in ovarian carcinoma cells leads to approximately 50% sensitization to x-ray radiation, as determined by the clonogenic ability assay. Our Western blotting and immunofluorescence analysis data also show that downregulation of CX3CR1 results in accumulation of DNA damage at lower doses. Thus, our data indicate that disruption of the CX3CR1 signaling could sensitize ovarian carcinoma to radiation therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3452. doi:1538-7445.AM2012-3452