Constitutive NF-kappaB activity in colorectal cancer cells: impact on radiation-induced NF-kappaB activity, radiosensitivity, and apoptosis.
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.
Voboril
R
R
Department of Cell and Molecular Biology, Center of Biomedical Sciences, Charles University 3rd Medical School, 100 00 Prague, Czech Republic. rene.voboril@seznam.cz
Weberova-Voborilova
J
J
D000230:Adenocarcinoma / Q000378:metabolism / Q000532:radiotherapy; D017209:Apoptosis / Q000528:radiation effects*; D020169:Caspases / Q000378:metabolism; D003037:Cobalt Radioisotopes; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects
D003037:Cobalt Radioisotopes; D016328:NF-kappa B; D020169:Caspases