李 新,周 原,龙福真,等.单酰基甘油脂肪酶对子宫内膜癌细胞迁移、侵袭和凋亡的影响[J].肿瘤学杂志,2024,30(11):939-945.
单酰基甘油脂肪酶对子宫内膜癌细胞迁移、侵袭和凋亡的影响
Effect of Monoacylglycerol Lipase on Migration, Invasion and Apoptosis of Endometrial Cancer Cells
投稿时间:2024-09-11  
DOI:10.11735/j.issn.1671-170X.2024.11.B008
中文关键词:  单酰基甘油脂肪酶  子宫内膜癌  脂质代谢  上皮-间充质转化  Bcl-2  Bax
英文关键词:monoacylglycerol lipase  endometrial cancer  lipid metabolism  epithelial-mesenchymal transition  Bcl-2  Bax
基金项目:山东省医药卫生科技发展计划项目(2019WS291)
作者单位
李 新 枣庄市立医院 
周 原 枣庄市立医院 
龙福真 枣庄市立医院 
金 童 枣庄市立医院 
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中文摘要:
      摘 要:[目的] 探讨单酰基甘油脂肪酶(monoacylglycerol lipase,MAGL)对子宫内膜癌细胞迁移、侵袭和凋亡的影响。[方法] 人子宫内膜癌细胞分为对照组(Normal组)和实验组(siRNA组和JZL184组),其中siRNA组分为阴性对照siControl组、siMAGL1组和siMAGL2组。采用Western blot检测子宫内膜癌细胞MAGL蛋白表达情况。采取不同浓度(0.1、1.0、5.0、10.0 μmol/L)JZL184处理子宫内膜癌细胞,利用噻唑蓝(methylthiazolyl tetrazolium,MTT)法检测细胞增殖能力,计算细胞增殖抑制率。应用小干扰RNA(siRNA)和JZL184分别构建敲除和抑制MAGL的子宫内膜癌细胞,采用Transwell实验检测细胞的迁移和侵袭能力,采用流式细胞术检测细胞的凋亡能力。采用qRT-PCR检测上皮-间充质转化(epithelial-mesenchymal transition,EMT)相关因子、Bcl-2及Bax基因表达情况,采用Western blot检测EMT相关因子、Bcl-2及Bax蛋白表达情况。[结果] 1.0 μmol/L JZL184对子宫内膜癌Ishikawa和RL95-2细胞增殖抑制率最大。JZL184组、siMAGL1组、siMAGL2组Ishikawa和RL95-2细胞迁移、侵袭数目均少于Normal组,差异均有统计学意义(P<0.05)。JZL184组、siMAGL1组、siMAGL2组Ishikawa和RL95-2细胞凋亡率均高于Normal组,差异均有统计学意义(P<0.05)。siMAGL1组、siMAGL2组Ishikawa和RL95-2细胞中上皮钙黏素(E-cadherin)基因相对表达量均高于Normal组和siControl组,波形蛋白(Vimentin)、Snail基因相对表达量及Bcl-2/Bax均低于Normal组和siControl组,差异均有统计学意义(P<0.05)。JZL184组Ishikawa、RL95-2细胞中E-cadherin、Bax蛋白相对表达量均高于Normal组,Vimentin、Snail、Bcl-2蛋白相对表达量均低于Normal组,差异均有统计学意义(P<0.05)。[结论] 下调MAGL表达可抑制子宫内膜癌细胞的迁移和侵袭能力,这可能是通过调控EMT相关因子的表达来实现的,MAGL可能通过调节子宫内膜癌细胞中Bcl-2和Bax的表达参与子宫内膜癌细胞凋亡。
英文摘要:
      Abstract: [Objective] To explore the effect of monoacylglycerol lipase (MAGL) on migration, invasion and apoptosis of endometrial cancer cells. [Methods] Human endometrial cancer cells were divided into a control group(Normal group) and an experimental group(siRNA group and JZL184 group), with the siRNA group being the negative control siControl group, siMAGL1 group, and siMAGL2 group. Ishikawa and RL95-2 cells were treated with different concentrations of MAGL inhibitor JZL184 (0.1, 1.0, 5.0 or 10.0 μmol/L), or transfected with the siMAGL1 and siMAGL2 to knock down the protein expression. The cell proliferation ability was detected by methylthiazolyl tetrazolium (MTT) assay, cell migration and invasion ability was detected by Transwell assay, cell apoptosis was detected by flow cytometry. The mRNA and protein expression of epithelial-mesenchymal transformation (EMT)- related factors, Bcl-2 and Bax was detected by qRT-PCR and Western blot, respectively. [Results] JZL184 at a concentratio of 1.0 μmol/L had the highest inhibitory rate on the proliferation of Ishikawa and RL95-2 cells. The migration and invasion ability of Ishikawa and RL95-2 cells in JZL184, siMAGL1 and siMAGL2 groups was significantly lower than that in control groups (P<0.05). The apoptosis rates of Ishikawa and RL95-2 cells in JZL184, siMAGL1 and siMAGL2 groups were higher than those in control groups (P<0.05). The expression of E-cadherin gene and protein in Ishikawa and RL95-2 cells of siMAGL1 and siMAGL2 groups were significantly higher than those of control groups; and the relative expression of Vimentin and Snail mRNA, and the Bcl-2/Bax were significantly lower than those of control groups (P<0.05). [Conclusion] Downregulation of MAGL expression can inhibit the migration and invasion ability of human endometrial cancer cells, which may be mediated by EMT-related factors. MAGL may be involved in the apoptosis of endometrial cancer cells by regulating the expression of Bcl-2 and Bax in endometrial cancer cells.
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