Exosomes Derived From Esophageal Cancer Cells Supress Their Radiosensitivity By Inhibiting BLID

[Objectives]Exosomes are extracellular nanoscale vesicles with sizes ranging from 30nm to 120nm formed through "endocytosis-fusion-outside" and a series of regulation and secreted by cells.Recently,an increasing number of scholars begin to study exosomes and try to explore how they work in tumor cells signal transmission.As we all know,tumor cells radioresistance is one of the most important factors leading to the decrease of local control and increase of distant metastasis of esophageal cancer patients.However,we barely know the roles exosomes play in tumor cells radiosensitivity.This study aims to investigate the amount of exsomes secreted by esophageal squamous cells(ESCC)after exposing to X rays and how these exosomes conversely influence the radiosensitivity of ESCC.In the mean time,we try to figure out these mechanisms and provide a solid support for exosomes biological functions and possible applications in the future.[Materials and methods]Exosomes were collected through gradient centrifugation and ultracentrifugation,then they were tested by nanoparticle tracking analysis and marker detection.We used PKH67 dye and Laser Scanning Confocal Microscope to observe the exosomes absorbed by ESCC.Flow Cytometer were applied to detect the proliferation and apoptosis of ESCC who absorbed the exosomes after exposing to X rays.Finally,western-blot and real-time quantitative per were used to explore the possible signal pathways and molecular mechanisms.[Results]Compared to the control group ESCC,ESCC exposed to X rays secreted greater amount of exosomes,which can be absorbed by other ECSS.Flow Cytometer results showed that compared to exosomes released by control group ESCC,exosomes released by ESCC exposed to X rays could significantly depress the apoptosis of ESCC and promote the radioresistance of ESCC.Western-blot and real-time quantitative pcr results suggested that the expressions of BLID and P-AKT in both exosomes from ESCC exposed to X rays and ESCC absorbed these exosomes were decreased.[Conclusion]This research demonstrated that esosomes released by ESCC after exposing to X rays could be absorbed by other ESCC,and depress the radiosensitivity of ESCC by reducing the expression of BLID and P-AKT.