Sensitization of colorectal cancer cells to irradiation by IL-4 and IL-10 is associated with inhibition of NF-kappaB.
The efficiency of radiotherapy for rectal cancer treatment is limited because of radioresistance. Transcription factor nuclear factor-kappaB (NF-kappaB), which has antiapoptotic properties, may play an important role in this process. Recent studies indicate that behavior of the tumor is done not only by oncogenic events in tumor cells but also by microenvironment surrounding the tumor. Therefore we tested anti-inflammatory cytokines IL-4 and IL-10 occurring in tumor stroma whether they can modulate response of colorectal cancer cells to irradiation and whether this potential effect is associated with NF- kappaB. SW620 colorectal cancer cells were used for all experiments. Cell growth and clonogenicity were determined by cell proliferation assay and clonogenic assay, respectively. Activation of NF-kappaB was assessed by ELISA-based transcription factor assay and luciferase reporter assay. Apoptosis was determined by measuring caspase 3 activity. Irradiation (2-8 Gy) inhibited growth and clonogenicity of SW620 cells, induced apoptosis, and activated NF-kappaB, predominantly its subunits p50, p65, and RelB. IL-4 or IL-10 (1, 10, 100 ng/ml) neither inhibited growth and clonogenicity nor activated NF-kappaB, but they sensitized cells to irradiation in a dose dependent manner. Radiosensitization by IL-4 or IL-10 was associated with inhibition of NF-kappaB, predominantly its subunits p50 and p65 and increased apoptosis. In conclusion, modulation of the intestinal microenvironment, high local concentration of anti-inflammatory cytokines such as IL-4 and IL-10 may help to overcome resistance of colorectal tumors to radiotherapy. In this process NF-kappaB may be employed.
Voboril
R
R
Department of Cell and Molecular Biology, Charles University 3rd Faculty of Medicine, Prague, Czech Republic. rene.voboril@seznam.cz
Weberova-Voborilova
J
J
D017209:Apoptosis / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011836:Radiation Tolerance / Q000502:physiology*
D016328:NF-kappa B; D016753:Interleukin-10; D015847:Interleukin-4; D053148:Caspase 3