Abstract 3942: Cell death resistance promoted by radiotherapy in a colorectal cell line

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Colorectal adenocarcinoma is the fourth more frequent cause of death by cancer in the world. Despite some similarities, the rectal cancer has characteristics that differentiate it from the colon cancer, resulting in different treatments and outcomes. The rectal cancer in stages II and III is treated with neoadjuvant chemoradiation followed by surgery, and the response to neoadjuvant treatment in patients is variable and unpredictable. Up to now, surgery intervention is required to assess the pathologic response to therapy. The identification of predictive biomarkers for response to therapy is of great importance, in order to identify the patients that will benefit from such treatment. To better understand the molecular alterations in cells that resist to the radiotherapy, we started our research using WiDr, a colon tumor cell line. Cell cycle synchronized WiDr cells were submitted to two cycles of irradiation (4Gy in each cycle and 2 week of interval between the cycles) and resistant cells were isolated. Irradiated WiDr cells (RxTWiDr) shown a better capacity to form colonies, in colony growth assays, when compared to parental WiDr cells. This characteristic was maintained when they were submitted to a new round of irradiation. In addition, WiDrRxT cells treated with Staurosporine presented a higher viability in MTT assays than WiDr cells. We also collected the conditioned medium (CM) from RxTWiDr and WiDr cells, and treated the parental WiDr cells. The parental cells treated with CM from RxTWiDr cells for 15 minutes shown an increase in the ERK1/2 activation when compared to cells treated CM from WiDr cells. These results demonstrated that radio resistant cells are more resilient than parental cells and that their secreted factors activated specific signaling pathways via ERK1/2 phosphorylation. The nature of these factors is under investigation using proteomics. Supported by Sao Paulo State Foundation (FAPESP) Citation Format: Antuani R. Baptistella, Bruna Rodrigues, Marcos Dias, Fernanda Giudice, Tonielli Lacerda, Tiago Santos, Felipe Silva, Petrus Paulo Silva, Samuel Aguiar, Vilma Martins. Cell death resistance promoted by radiotherapy in a colorectal cell line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3942. doi:10.1158/1538-7445.AM2014-3942