Cyclooxygenase-2 regulates the sensitivity of lung adenocarcinoma cells to ionizing radiation.

BLANCO, H.A.; ACQUIER, A.; PAZ, C.; MENDEZ, C.F.

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Investigación Clínica

Radioresistance is defined as a cell's capacityto survive after exposure to high energy radiation, a fact that may limittherapeutic options by reducing the efficacy of radiotherapy (Rt). Numeroustumor cells show a high expression of cyclooxygenase-2 (COX-2), a fact that hasbeen linked to more aggresive tumor phenotypes. Also, the COX-2 inhibitorcelecoxib (CXB) has been proposed as a possible Rt enhancer. We aim here toinvestigate whether COX-2 activity and expression regulate radiosensibility ina radioresistant lung adenocarcinoma-derived cell line (A549). Cells wereexposed to varying doses (0-10 Gy) of 60Co ionizing radiation (IR)in the presence or the absence of 7.5 mM CXB andradiosensitivity was determined using a standard clonogenic assay, cell cyclewas studied by flow cytometry after propidium iodide staining and MAPKsactivation and COX-2 expression by western blot using specific antibodies. IR produced a significant and dose-dependentreduction of cell viability showing an a/b ratio of 14.2 when calculated usingthe linear quadratic model, an effect that was significantly (p<0.05) enhancedby CXB. Rt (2.5 Gy) induced a clear G0/G1 phase accumulation and a reduction ofG2/M phase when compared to control (79.0 vs 68.0 and 9.0 vs 15.5% for Rt andcontrol, respectively), whereas CXB had no effect on cell cycle. CXB produced asignificant (p<0.05) and rapid activation of p38 and JNK (5 and 10 min afterexposure) but had no effect on COX-2 expression for up to 120 min as determinedby Western blot. Our results show that inhibition of COX-2 activityincreases the effect of IR in A549 cells without affecting cell cycleprogression although activating p38 and JNK. We conclude that COX-2 plays arole in the regulation of radiosensitivity of tumor cells in a mechanism thatincludes the participation of MAPKs.