Molecular radiobiologyAutophagy contributes to resistance of tumor cells to ionizing radiation
Section snippets
Materials and antibodies
Cell culture medium was from Gibco-Invitrogen (Karlsruhe-Germany). 3-Methyladenine (3-MA), chloroquine diphosphate (CQ), rapamycin, and anti-actin antibody were purchased from Sigma–Aldrich (Taufkirchen-Germany). Mouse monoclonal anti-LC3 antibody was purchased from nanoTools (Teningen, Germany).
Cell culture
Breast cancer cell lines MDA-MB-231 (MDA-231) and HBL-100 were used. Cells were cultures in RPMI Medium containing 10% fetal calf serum (FCS) and 1% penicillin–streptomycin and incubated in a humidified
Induction of autophagy by IR
To assess the effect of different radiation doses on the autophagic pathway the breast cancer cell lines MDA-231 and HBL-100, presenting significant different intrinsic IR sensitivities as previously reported from our laboratory [34] and shown in Fig. 1A, were analyzed at different time points after IR exposure (3, 7, and 24 h). As shown in Fig. 1B untreated radioresistant MDA-231 cells presented a low amount of LC3-II. However, exposure to IR at different doses (1, 2, and 4 Gy) markedly
Discussion
Autophagy is a catabolic mechanism used by cells to overcome different stress situations. On the one hand autophagy eliminates toxic and damaged cellular components. On the other hand this process delivers new precursors for synthesis of macromolecules. The interest in the recently discovered mechanism autophagy has increased in the last decade. Many studies have shown its importance by unraveling autophagy-dependent signaling in the development of various diseases, such as neurodegenerative
Acknowledgments
This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft (DFG, SFB-824/1), BMBF (MOBITUM, 01EZ0826; Kompetenzverbund Strahlenforschung, 03NUK007E; Spitzencluster m4, 01EX102C) awarded to GM. Further financial support was received from the Deutsche Forschungsgemeinschaft (SFB-773, TP-B02) awarded to H.P.R.
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