Role of mTOR pathway in modulation of radiation induced bystander effects

Abstract

Purpose

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.

Materials and methods

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.

Results

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.

Conclusions

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.

Keywords:

• Bystander effects
• cancer cells
• everolimus
• mTOR pathway
• radiation

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by grants from JNU in the form of UGC-SAP [F.3-12/2016/DRS-I]; DST PURSE [SR/Purse Phase-II/11(G)] and UPE-II [ID-80]. N.V. is thankful to UGC [23/12/2012(ii) EU-V] for fellowship.

Notes on contributors

Neha Verma

Neha Verma, Ph.D., is a researcher in Radiation and Cancer Therapeutics Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.

Ashu Bhan Tiku

Ashu Bhan Tiku, Ph.D., is a faculty and Head of Radiation and Cancer Therapeutics lab at School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.