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[1]高雅,赵洋,朱香熹,等.司美替尼对恶性周围神经鞘瘤细胞增殖和凋亡的影响[J].天津医科大学学报,2022,28(01):40-46.
　GAO Ya,ZHAO Yang,ZHU Xiang-xi,et al.The effect of selumetinib on cell proliferation and apoptosis of malignant peripheral nerve sheath tumor[J].Journal of Tianjin Medical University,2022,28(01):40-46.
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
28卷
期数:
2022年01期
页码:
40-46
栏目:
基础研究
出版日期:
2022-01-20

文章信息/Info

Title:
The effect of selumetinib on cell proliferation and apoptosis of malignant peripheral nerve sheath tumor
文章编号:
1006-8147（2022）01-0040-07
作者:
高雅1; 赵洋1; 朱香熹2; 赵玉龙1; 李光明1; 杨吉龙3; 叶帅4; 朱泽1
（1.天津医科大学基础医学院病原生物学系，天津300070；2.遵义医科大学珠海校区临床医学系，珠海519090；3.天津医科大学肿瘤医院骨与软组织肿瘤科，天津300060；4.天津医科大学总医院护理部，天津300050）
Author(s):
GAO Ya1; ZHAO Yang1; ZHU Xiang-xi2; ZHAO Yu-long1; LI Guang-ming1; YANG Ji-long3; YE Shuai4; ZHU Ze1
（1.Department of Pathogen Biology，School of Basic Medical Sciences，Tianjin Medical University，Tianjin 300070，China；2.Department of Clinical Medicine，Zhuhai Campus of Zunyi Medical University，Zhuhai 519090，China; 3.Department of Bone and Soft Tissue Oncology，Cancer Institute and Hospital，Tianjin Medical University，Tianjin 300060，China; 4. Department of nursing，General Hospital of Tianjin Medical University，Tianjin 300050，China）
关键词:
司美替尼; 恶性周围神经鞘瘤; H3K27me3; 增殖; 细胞凋亡
Keywords:
selumetinib; MPNST; H3K27me3; proliferation; apoptosis
分类号:
R739.43
DOI:
-
文献标志码:
A
摘要:
目的：探讨MEK1/2抑制剂司美替尼（selumetinib）对恶性周围神经鞘瘤（MPNST）细胞增殖和凋亡的影响及其机制。方法：用不同浓度的司美替尼处理细胞株ST88-14和STS26T，通过CCK-8、克隆形成、Transwell、细胞划痕、流式细胞术检测司美替尼对细胞增殖、凋亡、迁移和侵袭的影响。实时荧光定量PCR检测多梳抑制复合物2（PRC2）核心组分的mRNA表达水平。免疫印迹试验检测组蛋白3上的第27位赖氨酸的三甲基化（H3K27me3）的表达。结果：司美替尼抑制ST88-14、STS26T细胞增殖（t=16.44，P<0.05；t=16.21，P<0.05）、侵袭（t=10.51，P<0.05；t=8.44，P<0.05）、迁移（t=4.02，P<0.05；t=2.21，P<0.05）；与对照组相比，10 μmol/L和20 μmol/L司美替尼可使ST88-14、STS26T细胞凋亡率显著升高（t=14.64、10.10，均P<0.05；t=3.06、13.10，均P<0.05）；与对照组相比，司美替尼作用于ST88-14、STS26T细胞48 h，PRC2核心组分SUZ12和EZH2的mRNA水平显著升高（t=13.39、16.84，均P<0.05；t=6.10、12.93，均P<0.05）；与对照组相比，20 μmol/L司美替尼可显著增加ST88-14，STS26T细胞H3K27me3的表达（t=12.82，P<0.05；t=18.78，P<0.05）。结论：司美替尼通过促进H3K27me3表达抑制MPNST细胞的增殖，促进细胞凋亡。
Abstract:
Objective：To investigate the effects of selumetinib，a MEK1/2 inhibitor，on cell proliferation and apoptosis of malignant peripheral nerve sheath tumor（MPNST） and its mechanism. Methods: Cell lines ST88-14 and STS26T were treated with selumetinib at different concentrations，and the effects of selumetinib on cell proliferation，apoptosis，migration and invasion were detected by CCK-8 assay，colony formation assay，Transwell assay，cell scratch assay and flow cytometry.The mRNA expression level of each core component of PRC2 was detected by real-time fluorescence quantitative PCR. Western blotting assay was used to detect the expression of trimethylation of lysine 27 on histone 3（H3K27me3）. Results: Selumetinib inhibited the proliferation（t=16.44，P<0.05；t=16.21，P<0.05），invasion（t=10.51，P<0.05；t=8.44，P<0.05） and migration（t=4.02，P<0.05；t=2.21，P<0.05） of ST88-14，STS26T cells. Compared with the control group，the apoptosis rates of ST88-14 and STS26T cells were significantly increased when drug concentrations were 10 μmol/L and 20 μmol/L（t=14.64，10.10，both P<0.05; t=3.06，13.10，both P<0.05）. Compared with the control group，the mRNA levels of SUZ12 and EZH2，the core components of PRC2，were significantly increased by selumetinib for 48 h after treatment with ST88-14 and STS26T cells（t=13.39，16.84，both P<0.05；t=6.10，12.93，both P<0.05）. Compared with the control group，20 μmol/L selumetinib significantly increased the expression of H3K27me3 in ST88-14 and STS26T cells（t=12.82，P<0.05；t =18.78，P<0.05）. Conclusion: Selumetinib can inhibit the proliferation of MPNST cell lines and promote apoptosis by promoting the expression of H3K27me3.

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备注/Memo

备注/Memo:
基金项目 国家自然科学基金（81672650）
作者简介 高雅（1995-），女，硕士在读，研究方向：病原生物学；通信作者：朱泽，E-mail: zhuze@tmu.edu.cn。
更新日期/Last Update: 2022-01-20