肾上腺素能β2受体在三阴性乳腺癌细胞中的作用OA

Objective To investigate the effects of adrenergic receptors on the proliferation and migration of breast cancer cells and the underlying molecular mechanisms.Methods MTT assay and Transwell assay were used to detect the proliferation and migration of triple-negative breast cancer BT549 and HS578T cells treated with epineph⁃rine.CCLE database combined with RT-qPCR data was adopted to screen the highly expressed neurotransmitter recep⁃tor in breast cancer cells,namely β2-adrenergic receptor(ADRB2).MTT and Transwell assays were further per⁃formed to evaluate the proliferative and migratory capacities of triple-negative breast cancer cells treated with salbuta⁃mol,a specific agonist of ADRB2.Stable ADRB2-knockdown breast cancer cell lines were established to observe the regulatory effect of ADRB2 on cell proliferation and migration.RNA-seq data were analyzed to explore the molecular mechanisms triggered by adrenergic receptor activation,and the results were verified via Western blot.Results Com⁃pared with the control group(CTRL),the proliferation and migration of epinephrine-treated triple-negative breast can⁃cer BT549 and HS578T cells were significantly enhanced.ADRB2 was markedly overexpressed in triple-negative breast cancer cells.Salbutamol treatment also elevated the proliferative and migratory capacities of triple-negative breast cancer cells.In contrast to the PLKO group,both proliferation and migration were suppressed in the shADRB2#1 and shADRB2#2 groups.Finally,KEGG pathway enrichment analysis of differentially expressed genes between the control and epinephrine-treated breast cancer cell groups based on RNA-seq data revealed that adrenergic receptor acti⁃vation modulated the phosphorylation levels of multiple key molecules in the MAPK signaling pathway.Conclusion The ADRB2 activates the MAPK signaling pathway in breast cancer cells,thereby promoting their proliferation and mi⁃gration.