中国药物警戒 ›› 2018, Vol. 15 ›› Issue (9): 530-532.

• 垂体肿瘤治疗靶点及药物专栏 • 上一篇    下一篇

通路抑制对生长激素垂体腺瘤GH3细胞增殖的影响

杨晶晶, 冯洁, 赵斯达, 徐宁, 高华   

  1. 北京市神经外科研究所,北京 100050
  • 收稿日期:2018-11-02 修回日期:2018-11-02 出版日期:2018-09-20 发布日期:2018-11-02
  • 通讯作者: 高华,博士,副研究员,脑肿瘤的基础与临床研究。E-mail：huagao@aliyun.com
  • 作者简介:杨晶晶,专科,实验师,中枢神经系统肿瘤药物开发。
  • 基金资助:
    北京市自然科学基金(7162035):Notch通路及抑制剂在生长激素腺瘤发生发展的调控作用及机制的研究;北京市卫计委高层次人才计划(2015-3-040)

Effects of ERK1/2 Pathway Inhibitor U0126 on Cell Proliferation of Growth Homone Adenoma GH3 Cells

YANG Jingjng, FENG Jie,ZHAO Sida,XU Ning,GAO Hua   

  1. Beijing Neurosurgical Institute, Beijing 100050, China
  • Received:2018-11-02 Revised:2018-11-02 Online:2018-09-20 Published:2018-11-02

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摘要： 目的 观察ERK1/2通路抑制剂U0126对大鼠生长激素垂体腺瘤GH3细胞增殖的影响,以探索ERK1/2通路作为生长激素腺瘤潜在治疗靶点的可行性。方法 将大鼠GH3细胞分为对照组和U0126组,U0126组给予不同剂量（10、20、40 nM）的U0126,对照组给予等体积二甲基亚砜（DMSO）。细胞增殖实验（MTS法）检测细胞活力的变化;凋亡试剂盒检测细胞凋亡水平,Western-blot检测p-ERK1/2蛋白的水平。结果 与对照组相比,不同剂量U0126处理24 h的GH3细胞细胞活力分别下降14%、15%和19%;48 h下降19%、28%和36%;72 h下降24%、37%和52%。处理72 h后,U0126组膜联蛋白V（Annexin V）阳性细胞占总细胞数的比率分别为5.3%、11.4%和18.5%;碘化丙啶（PI）阳性细胞的比率分别为3.7%、7.3%和10.5%。处理24 h后U0126不同剂量组ERK的磷酸化蛋白表达水平呈下降趋势,40 nM组为对照组的41.7%,差异具有统计学意义（P <0.05）。结论 ERK1/2通路抑制剂可以诱导大鼠GH3细胞凋亡,抑制细胞增殖。

关键词: 生长激素腺瘤, 细胞活力, 凋亡, ERK1/2, U0126

Abstract: Objective To study the effect of ERK1/2 pathway inhibitor, U0126, on the cell proliferation and apoptosis of rat GH3 cell line, so as to explore ERK1/2 pathway as a potential therapy target for growth homone adenoma. Methods GH3 cells were divided into U0126 groups and control group. The U0126 groups were given different concentrations of U0126 (10, 20 and 40 nM), and control group was given the equal volume of dimethyl sulfoxide (DMSO). The proliferation of GH3 cells was determined by MTS experiment, and the apoptosis levels were detected by flow cytometry. The p-ERK1/2 levels were measured by western blot. ResultCompared to control group, the cell viability of U0126 (10, 20 and 40 nM) were decreased by 14%, 15% and 19% after 24 h; 19%, 28% and 36% after 48 h; 24%, 37% and 52% after 72 h, respectively. After 72 h treatment, Annexin V positive cells in U0126 groups were 5.3%, 11.4% and 18.5%, and propidium iodide (PI) positive cells were 3.7%, 7.3% and 10.5%. The level of p-ERK protein in U0126 groups was decreased than that of control group, and 40 nM group was 41.7% of that in the control group. The difference was statistically significant (P <0.05). Conclusion The ERK1/2 pathway inhibitors, U0126, can induce apoptosis and inhibit cell proliferation in rat GH3 cells line.

Key words: growth homone adenoma, cell viability, apoptosis, ERK1/2 pathway, U0126

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