Constitutive NF-kappaB activity in colorectal cancer cells: impact on radiation-induced NF-kappaB activity, radiosensitivity, and apoptosis
Abstrakt
Constitutive NF-kappa B activity has been found in many cancer cells of different origin. in our study we focused on constitutive NF-kappa B activity and its impact on radiation-induced NF-kappa B 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-kappa B activity.
Moreover, irradiation caused secondary NF-kappa B 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-kappa B activity and radiation-induced NF-kappa B activity (r=0.835), the level of constitutive NF-kappa B activity predicted the level of secondary, radiation-induced NF-kappa B activity. Furthermore, SW620 cells with the highest level of constitutive NF-kappa B activity displayed the lowest radiosensitivity and the lowest level of spontaneous apoptosis; Caco-2 cells with almost undetectable level of constitutive NF-kappa B activity displayed the highest radiosensitivity and even highest level of spontaneous apoptosis.
SW480 cells showed intermediate level of constitutive NF-kappa B activity, intermediate radiosensitivity and intermediate level of spontaneous apoptosis. Our data suggest that the level of constitutive NF-kappa B activity may predict radiosensitivity of colorectal cancer cells.
Such prediction may allow the individualization of patient treatment by radiotherapy