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碱性亮氨酸拉链和W2结构域2对子宫内膜癌细胞生物学行为的作用及机制

Role of basic leucine zipper and W2 domains 2 on the biological behaviors of endometrial cancer cells and its mechanism

    摘要
  • 摘要:
    目的 探讨碱性亮氨酸拉链和W2结构域2(BZW2)对子宫内膜癌细胞增殖、侵袭、迁移及细胞周期的调控作用及其潜在作用机制。
    方法 采用实时荧光定量聚合酶链反应(RT-qPCR)、蛋白质印迹法(Western blot)检测BZW2在人子宫内膜基质细胞系ESC和人子宫内膜癌细胞(Ishikawa、KLE、RL95-2、HEC-1-A)中的表达。将BZW2干扰质粒转染至HEC-1-A细胞，并加入Wnt/β-连环蛋白(Wnt/β-catenin)信号通路激动剂SKL2001进行处理。采用CCK-8、克隆形成实验、划痕实验及Transwell实验分别检测细胞活性、克隆形成、迁移及侵袭能力; 采用流式细胞术检测细胞周期; 采用GSEA分析BZW2在Wnt信号通路中的富集度; 采用Western blot分析增殖、转移、周期及Wnt/β-catenin通路相关蛋白表达水平。
    结果 BZW2在子宫内膜癌细胞中表达上调，干扰BZW2可抑制子宫内膜癌细胞增殖、迁移、侵袭，并诱导G0/G1期细胞阻滞(P < 0.001)。敲低BZW2可使Wnt/β-catenin通路失活(P < 0.001), SKL2001可部分逆转BZW2缺失对HEC-1-A细胞增殖、迁移、侵袭及细胞周期的调控作用(P < 0.001)。
    结论 BZW2下调可抑制子宫内膜癌细胞增殖、侵袭、迁移，并促进G0/G1期细胞阻滞，其机制可能与Wnt/β-catenin信号通路失活有关, BZW2可作为治疗子宫内膜癌的新靶点。

     

    Abstract:
    Objective To investigate the regulatory effects of basic leucine zipper and W2 domains 2 (BZW2) on proliferation, invasion, migration and cell cycle of endometrial cancer cells and its potential action mechanism.
    Methods Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the expression of BZW2 in human endometrial stromal cell line ESC and human endometrial cancer cells (Ishikawa, KLE, RL95-2, HEC-1-A). BZW2 interference plasmid was transfected into HEC-1-A cells and treated with Wnt/β-catenin signaling pathway agonist SKL2001. CCK-8, clone formation assay, scratch assay and Transwell assay were used to detect cell activity, colony formation, migration and invasion ability, respectively; the cell cycle was detected by flow cytometry; the concentration of BZW2 in Wnt signaling pathway was analyzed by GSEA; the levels of proliferation, metastasis, cycle and Wnt/β-catenin pathway-related proteins were analyzed by Western blot.
    Results The expression of BZW2 was up-regulated in endometrial cancer cells, and interference with BZW2 inhibited the proliferation, migration and invasion of endometrial cancer cells, and induced G0/G1 cell arrest (P < 0.001). BZW2 knockdown inactivated the Wnt/β-catenin pathway (P < 0.001), and SKL2001 partially reversed the regulatory effects of BZW2 loss on the proliferation, migration, invasion and cell cycle of HEP-1-A cells (P < 0.001).
    Conclusion Down-regulation of BZW2 can inhibit the proliferation, invasion and migration of endometrial cancer cells, and promote G0/G1 cell arrest, which may be related to the inactivation of Wnt/β-catenin signaling pathway. BZW2 may be a new target for the treatment of endometrial cancer.

     

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