TY  - JOUR
A1  - Kuger, Sebastian
A1  - Cörek, Emre
A1  - Polat, Bülent
A1  - Kämmerer, Ulrike
A1  - Flentje, Michael
A1  - Djuzenova, Cholpon S.
T1  - Novel PI3K and mTOR Inhibitor NVP-BEZ235 Radiosensitizes Breast Cancer Cell Lines under Normoxic and Hypoxic Conditions
N2  - In the present study, we assessed, if the novel dual phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor NVP-BEZ235 radiosensitizes triple negative (TN) MDA-MB-231 and estrogen receptor (ER) positive MCF-7 cells to ionizing radiation under various oxygen conditions, simulating different microenvironments as occurring in the majority of breast cancers (BCs). Irradiation (IR) of BC cells cultivated in hypoxic conditions revealed increased radioresistance compared to normoxic controls. Treatment with NVP-BEZ235 completely circumvented this hypoxia-induced effects and radiosensitized normoxic, reoxygenated, and hypoxic cells to similar extents. Furthermore, NVP-BEZ235 treatment suppressed HIF-1α expression and PI3K/mTOR signaling, induced autophagy, and caused protracted DNA damage repair in both cell lines in all tested oxygen conditions. Moreover, after incubation with NVP-BEZ235, MCF-7 cells revealed depletion of phospho-AKT and considerable signs of apoptosis, which were signifi-cantly enhanced by radiation. Our findings clearly demonstrate that NVP-BEZ235 has a clinical relevant potential as a radiosensitizer in BC treatment.
KW  - Novel PI3K
KW  - NVP-BEZ235
KW  - mTOR Inhibitor
KW  - radiosensibility
KW  - Akt
KW  - DNA repair protraction
KW  - apoptosis
KW  - hypoxia
KW  - autophagy
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112708
ER  -