Objective: To investigate the effect of BIX01294 (BIX), a methyltransferase inhibitor, on the migration and decidualization of the stromal cells in mouse uterus.
Methods: Mouse endometrial stromal cells were isolated and cultured from the uterus of pregnant mice on day 3.5 of gestation. The migration and decidualization of mouse endometrial stromal cells treated with BIX at different concentrations were observed with wound healing assay and real-time PCR.
Results: The migration distance of mouse endometrial stromal cells increased as the BIX concentration increased within the range below 15 µmol/L. Compared with the control cells, the cells treated with BIX (15 µmol/L) showed significantly increased migration distances, but increasing BIX concentration to 20 µmol/L did not further increase the cell migration distance and began to cause cell death. Compared with the control cells, the BIX-treated stromal cells exhibited significantly down-regulated expression of Ehmt2 mRNA, and 15 µmol/L BIX caused inhibition of decidualization in the stromal cells.
Conclusion: Within a defined concentration range, BIX promotes the migration and inhibits decidualization of mouse uterine stromal cells by inhibiting the expression of Ehmt2 mRNA.
目的: 探讨甲基化转移酶抑制剂BIX01294（BIX）对小鼠子宫内膜基质细胞迁移和蜕膜化过程的作用和影响。
方法: 取妊娠第3.5天小鼠子宫分离培养得小鼠子宫内膜基质细胞，采用细胞划痕运动分析、体外诱导小鼠子宫内膜基质细胞蜕膜化模型及Real-time PCR方法分别从形态学和分子生物学角度观察BIX对小鼠子宫内膜基质细胞迁移及蜕膜化的影响。
结果: 在一定浓度范围内（BIX≤15 μmol/L），小鼠子宫内膜基质细胞的迁移距离随着BIX浓度的升高而增加，与对照组相比，BIX 15 μmol/L处理组基质细胞的迁移距离增加最明显，差异具有统计学意义，当BIX浓度提高到20 μmol/L时，细胞迁移距离增加不明显，且此时开始出现细胞的死亡；与对照组相比，BIX处理24 h组小鼠子宫内膜基质细胞Ehmt2 mRNA表达显著下调（P < 0.01）；并且15 μmol/L BIX能够抑制小鼠子宫内膜基质细胞蜕膜化反应。
结论: 一定浓度范围的BIX通过抑制Ehmt2 mRNA在基质细胞中的表达促进小鼠子宫内膜基质细胞的迁移，并且对小鼠子宫基质细胞的蜕膜化过程有抑制作用。