Bromocriptine Promote The Secretion Of Exosomes And The Role Of Exosomes In Drug Sensitivity Of Rat Prolactinoma MMQ Cells In Vitro

Objective:To investigate the effect of bromocriptine on the secretion of exosomes and the role of exosomes in drug sensitivity of rat prolactinoma MMQ cells.Methods:The toxicity of bromocriptine on MMQ cells was detected by CCK-8 assay,and the half inhibitory concentration(IC₅₀)was determined.Prolactinoma MMQ cells were exposed to bromocriptine for48 h.Exosomes were isolated by differential centrifugation and detected on the basis of morphology and the presence of exosomal markers.The process of exosomes being taken up by MMQ cells was observed by laser confocal microscopy;The ability of exosomes to regulate bromocriptine sensitivity was tested by cell-viability and real-time quantitative PCR assays.The expression levels of PR domain zinc finger protein 2?PRDM2?,dopamine 2 receptor?D2R?,and ERK1/2,and p-ERK1/2 were determined by western blotting.Results:The IC₅₀0 of bromocriptine on MMQ cells was 52.91?mol/L.The particles and protein in exosomes collected from treatment of MMQ cells with 50?mol/L of bromocriptine were significantly increased compared to exosomes collected from MMQ cells not treated with bromocriptine?all P<0.01?.Exosomes labeled with PKH67 showed that exosomes collected from bromocriptine treatment of MMQ cells were uptaken by normal MMQ cells.After exosomes absorbed by normal MMQ cells,on the one hand,the half-maximal inhibitory concentration(IC₅₀)of bromocriptine was increased for MMQ cells?P<0.01?.The exosome-treated MMQ cells exhibited lower PRDM2 and D2R expression levels?all P<0.05?but higher p-ERK1/2 expression levels than the control group?P<0.05?.Conclusion:Bromocriptine promote the secretion of exosomes in MMQ cells and the exosomes produced by pituitary prolactinomas after the treatment of bromocriptine may be involved in the transmission of information through cell-cell communication,which can make certain prolactinomas MMQ cells obtain drug resistance.