Constitutive NF-kappaB activity has been found in many cancer cells of different origin. In our study we focused on constitutive NF-kappaB activity and its impact on radiation-induced NF-kappaB activity, intrinsic radiosensitivity, and apoptosis. Using colorectal cancer cell lines (Caco-2, SW480, SW620) we demonstrated that each cell line expresses different level of constitutive NF-kappaB activity. Moreover, irradiation caused secondary NF-kappaB activation which differed in each cell line. The cell lines tested displayed also different intrinsic radiosensitivities as was determined by clonogenic assay, and different spontaneous and radiation-induced apoptosis determined by activity of caspase 3. Complex analysis of our results revealed that there was a strong correlation between constitutive NF-kappaB activity and radiation-induced NF-kappaB activity (r=0.835), the level of constitutive NF-kappaB activity predicted the level of secondary, radiation-induced NF-kappaB activity. Furthermore, SW620 cells with the highest level of constitutive NF-kappaB activity displayed the lowest radiosensitivity and the lowest level of spontaneous apoptosis; Caco-2 cells with almost undetectable level of constitutive NF-kappaB activity displayed the highest radiosensitivity and even highest level of spontaneous apoptosis. SW480 cells showed intermediate level of constitutive NF-kappaB activity, intermediate radiosensitivity and intermediate level of spontaneous apoptosis. Our data suggest that the level of constitutive NF-kappaB activity may predict radiosensitivity of colorectal cancer cells. Such prediction may allow the individualization of patient treatment by radiotherapy.

Department of Cell and Molecular Biology Center of Biomedical Sciences Charles University 3rd Medical School 100 00 Prague Czech Republic

Dissociated invasively growing cancer cells with NF-kappaB/p65 positivity after radiotherapy: a new marker for worse clinical outcome in rectal cancer? Preliminary data