Role of mTOR pathway in modulation of radiation induced bystander effects.

Radiation-induced bystander effect (RIBE) is considered as an important consequence of radiation exposure. Based on the type of effect induced, it has important implications in radiation therapy. mTOR pathway, a key regulator of cell survival, plays an important role in radiation-induced damages. However, the role of mTOR signaling in the modulation of RIBE is still unclear. We evaluated the role of mTOR pathway in RIBE and its relationship with the radiation response of target cells. Direct and bystander effects were evaluated by using clonogenic and MTT assay in five different cell lines. Expression of mTOR pathway proteins in directly targeted and bystander cells was studied using western blotting. Among five different cell lines naïve HT1080 and A549 cells exhibited proliferative bystander effect induced by conditioned media and irradiated conditioned media, while no effect was observed in other cell lines. Everolimus significantly abolished the proliferative bystander effect induced in naïve cells. These results suggested that the mTOR pathway plays an important role in RIBEs. These effects are cell type-specific and depending on the radiosensitivity of the target cells, therapeutic benefits of radiation may be modulated by treatment with mTOR inhibitors.