Bystander effects induced by electron beam‑irradiated MCF‑7 cells: a potential mechanism of therapy resistance

Feghhi, M and Jabbari, N and Mostafanezhad, K and Rezaie, J (2021) Bystander effects induced by electron beam‑irradiated MCF‑7 cells: a potential mechanism of therapy resistance. Breast Cancer Research and Treatment, 187. pp. 657-671.

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Abstract

The distinct direct and non-targeting effects of electron beam radiation on MCF-7 cells remain obscure. We aimed to investigate the effect of electron beam irradiation (EBI) and conditioned media (CM) of the irradiated MCF-7 cells on MCF-7 cells. The cytotoxic effects of CM from irradiated MCF-7 cells on the mesenchymal stem cells and human umbilical vein endothelial cells (HUVECs) were also examined. Methods Cell viability and apoptosis were assayed via MTT and flow cytometry analysis, respectively. The production of ROS (reactive oxygen species) was evaluated by the chemical fluorometric method, while the amount of extracellular vesicles was detected via acetylcholinesterase activity assay. Expression of genes involved in apoptosis, including caspase-3, -8, -9, and stemness such as Sox-2 and Oct-4, were calculated through qPCR. The wound healing rate of cells was monitored via in vitro scratch assay. Results Compared to the control group, EBI groups showed decreased cell viability but increased apoptosis and ROS as well as acetylcholinesterase activity dose-dependently (P < 0.05). Concurrently with increasing the dose of the electron beam, the transcript levels of apoptotic genes (caspase-3, -8, -9) and stemness-related genes (Sox-2 and Oct-4) were up-regulated following EBI. The wound healing rate of irradiated MCF-7 cells increased dose-dependently (P < 0.05). Similar results were observed after treatment with CM from irradiated MCF-7 cells. Additionally, CM from irradiated MCF-7 cells decreased the viability of MCF-7 cells, mesenchymal stem cells, and HUVECs (P < 0.05). Conclusion MCF-7 cells treated with an electron beam and CMs from irradiated MCF-7 cells exhibit an up-regulation in both genes involved in the apoptosis pathway and stemness. As a result, EBI can affect apoptosis and stemness in MCF-7 cells in direct and bystander manners. However, specific signaling pathways require careful evaluation to provide an understanding of the mechanisms involved in the EBI-induced alternation in tumor cell dynamics

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