摘要
目的基于转化生长因子-β1(TGF-β1)/神经生长因子(NGF)轴探讨右美托咪定(Dex)对人子宫肌瘤细胞增殖和凋亡的影响。方法将人子宫平滑肌瘤SK-UT-1细胞分为对照组,TGF-β1激活剂组(SRI-011381组),Dex1 nmol/L、Dex 10 nmol/L、Dex 100 nmol/L组,Dex100+SRI-011381组。使用CCK8法、克隆形成实验、流式细胞术、划痕实验、Transwell实验检测细胞活力、增殖、凋亡、迁移和侵袭情况;RT-qPCR检测细胞增殖相关基因[增殖细胞核抗原(PCNA)、细胞周期蛋白D1(Cyclin D1)]和凋亡相关基因[半胱天冬酶-9(Caspase-9)、Bcl-2相关x蛋白(Bax)/B细胞淋巴瘤-2(Bcl-2)]表达;Western blot检测细胞TGF-β1/NGF轴相关蛋白[TGF-β1、磷酸化(p)-Smad3、Smad3、NGF、酪氨酸受体激酶A(TrkA)、p75神经营养因子受体(p75 NTR)]表达水平。结果与对照组相比,不同浓度Dex组细胞活力、克隆数量、迁移率、侵袭数、增殖相关基因表达、TGF-β1/NGF轴相关蛋白表达水平显著降低(P<0.05),凋亡相关基因表达水平显著升高(P<0.05);SRI-011381组细胞上述指标结果与之相反(P<0.05)。与Dex 100 nmol/L组相比,Dex100+SRI-011381组细胞活力、克隆数量、迁移率、侵袭数、增殖相关基因表达、TGF-β1/NGF轴相关蛋白表达水平显著升高(P<0.05),凋亡相关基因表达水平显著降低(P<0.05)。结论Dex能抑制子宫肌瘤细胞增殖、迁移和侵袭,促进细胞凋亡,其作用机制可能与抑制TGF-β1/NGF轴有关。
Objective To investigate the effects of dexmedetomidine(Dex)on the proliferation and apoptosis of human uterin leiomyoma cells based on the transforming growth factor-β1(TGF-β1)/nerve growth factor(NGF)axis.Methods Human uterine leiomyoma SK-UT-1 cells were divided into control group,TGF-β1 activator group(SRI-011381 group),Dex 1 nmol/L,Dex 10 nmol/L,Dex 100 nmol/L groups and Dex100+SRI-011381 group.CCK8 assay,clone formation experiment,flow cytometry,wound healing assay,and Transwell experiment were conducted to assess cell viability,proliferation,apoptosis,migration,and invasion.RT-qPCR was used to detect the expression of cell proliferation-related genes[proliferating cell nuclear antigen(PCNA),Cyclin D1]and apoptosis-related genes[Caspase-9,Bcl2-associated x protein(Bax)/B-cell lymphoma-2(Bcl-2)].Western blot was employed to detect the expression levels of proteins related to the TGF-β1/NGF axis[TGF-β1,phosphorylated(p)-Smad3,Smad3,NGF,tropomyosin receptor kinase A(TrkA),p75 neurotrophin receptor(p75 NTR)]in the cells.Results Compared with the control group,the cell viability,clone number,migration rate,invasion count,proliferation-related genes expression,and the expression levels of proteins related to the TGF-β1/NGF axis were significantly decreased(P<0.05),while the expression of apoptosis-related genes were significantly increased(P<0.05)in the groups treated with different concentrations of Dex.Conversely,the results for these indicators were opposite in the SRI-011381 group(P<0.05).Compared with the Dex 100 nmol/L group,the cell viability,clone number,migration rate,invasion count,proliferation-related genes expression,and the expression levels of proteins related to the TGF-β1/NGF axis were significantly increased(P<0.05),while the expression of apoptosis-related genes were significantly decreased(P<0.05)in the Dex 100+SRI-011381 group.Conclusion Dexmedetomidine can inhibite the proliferation,migration and invasion of uterine leiomyoma cells and promote cell apoptosis,and its mechanism of action may be related to the inhibition of the TGF-β1/NGF axis.
作者
戎瑞爽
李燕
李梅
王洋
李赫
尹会文
RONG Ruishuang;LI Yan;LI Mei;WNAG Yang;LI He;YIN Huiwen(Anesthesiology Department,The Second People's Hospital of Hengshui,Hengshui,Hebei 053000,China;Gynecology Department,The Second People's Hospital of Hengshui,Hengshui,Hebei 053000,China;Gland Surgery,The Second People's Hospital of Hengshui,Hengshui,Hebei 053000,China;Obstetrics and Gynecology,The Second People's Hospital of Hengshui,Hengshui,Hebei 053000,China;Infection Department,The Second People's Hospital of Hengshui,Hengshui,Hebei 053000,China)
出处
《中国优生与遗传杂志》
2025年第9期1919-1926,共8页
Chinese Journal of Birth Health & Heredity
基金
衡水市2024年度第一批科技计划(自筹经费)项目(2024014003Z)。
