Department of Neurosurgery, Jiangsu University Affiliated People's Hospital.
Department of Neurosurgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaiyin, China.
J Cell Biochem. 2019 Aug;120(8):13310-13320. doi: 10.1002/jcb.28605. Epub 2019 Mar 27.
Glioma is characterized by cell over-proliferation, aggressive phenotype, and angiogenesis. B cell translocation gene 1 (BTG1) works as a tumor suppressor in various cancer types. We aimed to study the functions of BTG1 in glioma development.
We tested the BTG1 expressions in various glioma cell lines. T98G and U87 cells were transfected with siBTG1 and BTG1 expression vector, respectively, then assessing cell viability, cell migration, and invasion abilities. Flow cytometry was performed to analyze apoptosis and cell cycle distribution. The status of angiogenesis was assessed by In vitro angiogenesis assay. Quantitative polymerase chain reaction and Western blot analysis were used for expression analyses. The inhibitor FH535 (20 μM) and agonist LiCl (20 mM) of the Wnt/β-catenin pathway were introduced to treat transfected cells.
BTG1 was low-expressed in glioma cell lines. In T98G cell transfected with siBTG1, cell proliferation, migration, invasion, and angiogenesis abilities were notably increased, BTG1 silencing promoted the cell survival and cell cycle progression from G0/G1 to the S phase. In BTG overexpressed U87 cell, cell proliferation, migration, invasion, and angiogenesis abilities were significantly inhibited. In addition, cell apoptosis significantly increased and the number of G0/G1 phase cells was also significantly increased. We also found that the activation of Wnt/β-catenin was significantly inhibited in BTG1 group. LiCl and FH535 treatments could partially reverse the effects of BTG1 on glioma cell viabilities.
Our data suggested that BTG1 functions as a tumor suppressor in glioma, and the anticancer ability of BTG1 involves the repression of the Wnt/β-catenin pathway.
神经胶质瘤的特征是细胞过度增殖、侵袭性表型和血管生成。B 细胞易位基因 1（BTG1）在多种癌症类型中作为肿瘤抑制因子发挥作用。我们旨在研究 BTG1 在神经胶质瘤发展中的作用。
我们检测了各种神经胶质瘤细胞系中的 BTG1 表达。用 siBTG1 和 BTG1 表达载体分别转染 T98G 和 U87 细胞，然后评估细胞活力、细胞迁移和侵袭能力。流式细胞术分析细胞凋亡和细胞周期分布。体外血管生成实验评估血管生成状态。定量聚合酶链反应和 Western blot 分析用于表达分析。引入 Wnt/β-catenin 通路的抑制剂 FH535（20μM）和激动剂 LiCl（20mM）处理转染细胞。
BTG1 在神经胶质瘤细胞系中低表达。在转染 siBTG1 的 T98G 细胞中，细胞增殖、迁移、侵袭和血管生成能力显著增加，BTG1 沉默促进细胞从 G0/G1 期向 S 期存活和细胞周期进展。在 BTG1 过表达的 U87 细胞中，细胞增殖、迁移、侵袭和血管生成能力显著受到抑制。此外，细胞凋亡显著增加，G0/G1 期细胞数量也显著增加。我们还发现 BTG1 组中 Wnt/β-catenin 的激活明显受到抑制。LiCl 和 FH535 处理可部分逆转 BTG1 对神经胶质瘤细胞活力的影响。
我们的数据表明，BTG1 在神经胶质瘤中起肿瘤抑制因子的作用，BTG1 的抗癌作用涉及对 Wnt/β-catenin 通路的抑制。
