Although radiation therapy is one of the choices to treat cancers and is an excellent local treatment method, existence of radiation resistant cell is a major problem. We established clinically relevant radioresistant (CRR) cells that can survive exposing to 2 Gy/day X-rays for more than 30 days. However, the mechanism to obtain resistance has not been elucidated yet. We investigated the relationships between resistant mechanism to hydrogen peroxide (H2O2) and plasma membrane state in CRR cells.
CRR cells showed resistance to H2O2, but catalase enzyme activity was down-regulated. Plasma membrane potential were low, no internal H2O2 increase and no lipid peroxidation were seen even after 2 hours of H2O2 treatment in CRR cells. Administration of oxidized lipid led to further cell death after H2O2 treatment in CRR cells. The lipoxygenase (ALOX) gene and protein expressions were down-regulated in CRR cells. We also established stress-sensitive ρ0 cells that lack mitochondrial DNA. Gene and protein expressions of ALOX were up-regulated in ρ0 cells. Expression of cyclooxygenase-2 does not seem to be involved in this mechanism.
These results suggest that the involvement of ALOX in resistance or sensitivity of cancer treatment.
