医学新知2026，Vol.36Issue(2)：179-187,9.DOI:10.12173/j.issn.1004-5511.202504171
低浓度右美托咪定经ERK1/2依赖方式促进TRIO、PKN2和CKAP5介导的骨肉瘤细胞增殖和侵袭
Low-concentration Dexmedetomidine promotes the proliferation and invasion of osteosarcoma cells mediated by TRIO,PKN2 and CKAP5 via ERK1/2-dependent activation
摘要
Abstract
Objective To investigate the effect of Dexmedetomidine(Dex)on osteosarcoma(OS)cells and its underlying mechanism.Methods The optimal exposure concentrations of Dex,α2-adrenergic receptor(α2-AR)antagonist,PKA inhibitor,and ERK1/2 inhibitor were determined by MTT assay.Genes positively correlated with ERK1/2 expression in OS samples and potentially mediating its tumor-promoting effect were extracted from the GEPIA database,and their expression levels in OS cells were verified by qRT-PCR and Western blot.After silencing candidate genes with siRNA,MTT assay,flow cytometry,Transwell assay,and colony formation assay were performed to evaluate the role of ERK1/2 pathway genes in the processes by which Dex affects OS cell proliferation,apoptosis,invasion,and colony formation ability.Results 25 nM Dex was the optimal concentration for promoting OS cell viability.The ERK1/2 inhibitor(Ravoxertinib)significantly antagonized the enhancement of OS cell viability induced by low-concentration Dex,whereas inhibition of α2-AR or PKA exerted weaker effects.Bioinformatics analysis identified that TRIO,PKN2,CKAP5,and NEK4 were highly associated with the oncogenic function of ERK1/2 in OS.Western blot demonstrated that Ravoxertinib blocked the upregulation of TRIO,PKN2,CKAP5,and NEK4 induced by Dex.Silencing TRIO,PKN2,or CKAP5 effectively suppressed Dex-induced increases in OS cell viability,invasion capacity,and colony formation,while attenuating the inhibitory effect of Dex on cell apoptosis.Conclusion Low-concentration Dex upregulates the expression of TRIO,PKN2,and CKAP5 in an ERK1/2-dependent manner,thereby promoting the malignant biological potential of OS cells.关键词
右美托咪定/骨肉瘤/TRIO/PKN2/CKAP5/ERK1/2 通路Key words
Dexmedetomidine/Osteosarcoma/TRIO/PKN2/CKAP5/ERK1/2 pathway分类
医药卫生引用本文复制引用
杨会,陈磊杰,赵敏,王忠慧,廖珊,陈帘璞,龚玲俐,李珊珊..低浓度右美托咪定经ERK1/2依赖方式促进TRIO、PKN2和CKAP5介导的骨肉瘤细胞增殖和侵袭[J].医学新知,2026,36(2):179-187,9.基金项目
云南省教育厅科学研究基金项目(2024J0258、2023Y0656) （2024J0258、2023Y0656）
云南省科技厅-昆明医科大学应用基础研究联合专项基金项目(202401AY070001-153) （202401AY070001-153）
云南省科技厅基础研究计划项目(202501AT070133) （202501AT070133）
云南省省级临床医学中心科研项目(2024YNLCYXZX0550) （2024YNLCYXZX0550）
昆明医科大学第二附属医院院内科技计划项目(2022yk09) （2022yk09）
云南省高层次卫生健康技术人才项目(H-2024036) （H-2024036）
