中国药物警戒 ›› 2018, Vol. 15 ›› Issue (4): 193-196.

• 基础与临床研究 •    下一篇

TGF-β/Smad3信号通路在氟维司群抑制泌乳素腺瘤MMQ细胞增殖和分泌中的作用

刘潜1, 李振业2, 曹磊2, 高华1, 李储忠1, 张亚卓1,*   

  1. 1北京市神经外科研究所,北京 100050;
    2北京天坛医院,北京 100050
  • 收稿日期:2018-05-29 修回日期:2018-05-29 出版日期:2018-04-20 发布日期:2018-05-29
  • 通讯作者: 张亚卓,男,主任医师,教授·博导,中枢神经系统肿瘤的基础和临床研究。E-mail:zyz2004520@yeah.net
  • 作者简介:刘潜,女,博士,中枢神经系统肿瘤及分子药理研究。
  • 基金资助:
    国家自然科学基金(81502154):EGFL7调控EGFR介导的Akt/MAPK通路促进垂体腺瘤侵袭及机制研究; 国家自然科学基金(81601205):TGF-β通路在生长激素腺瘤侵袭与激素分泌中的作用及机制研究

Effects of TGF-β/Smad3 Pathway on Process of Fulvestrant Inhibiting Proliferation and Secretion of Prolactinoma MMQ Cells

LIU Qian1, LI Zhen-ye2, CAO Lei2, GAO Hua1, LI Chu-zhong1, ZHANG Ya-zhuo1,*   

  1. 1Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China;
    2Beijing Tiantan Hospital of Capital Medical University, Beijing 100050, China
  • Received:2018-05-29 Revised:2018-05-29 Online:2018-04-20 Published:2018-05-29

摘要: 目的 观察氟维司群对泌乳素腺瘤MMQ细胞增殖和分泌的影响,探讨TGF-β/Smad3信号通路在其中的作用。方法 MTS试验检测不同浓度氟维司群处理泌乳素腺瘤MMQ细胞24、48、72 h后细胞增殖活力。ELISA检测不同浓度的氟维司群处理泌乳素腺瘤MMQ细胞24 h后细胞上清中TGF-β1和泌乳素的分泌水平。免疫荧光检测泌乳素腺瘤MMQ细胞经氟维司群处理24 h后细胞中磷酸化Smad3的表达水平。结果 氟维司群能够有效抑制泌乳素腺瘤MMQ细胞的增殖,并呈现良好的时间依赖性与浓度依赖性。氟维司群处理泌乳素腺瘤MMQ细胞可显著提高活性TGF-β1水平、降低泌乳素水平,呈现良好的剂量依赖作用。免疫荧光技术观察氟维司群处理泌乳素腺瘤MMQ细胞24 h后,细胞核和细胞浆中(主要为细胞核中)p-Smad3明显增多。结论 氟维司群可能通过TGF-β/Smad3信号通路抑制泌乳素腺瘤MMQ细胞增殖和泌乳素分泌。

关键词: 氟维司群, 雌激素受体拮抗剂, TGF-β, /Smad3信号通路, 泌乳素腺瘤, MMQ细胞

Abstract: Objective To study the effects of TGF-β/Smad3 pathway on process of fulvestrant inhibiting the proliferation and secretion of prolactinoma MMQ cells. Methods After treated with different concentrations of fulvestrant for 24, 48, 72 h, the proliferation of prolactinoma MMQ cells was determined by MTS. Simultaneously, the active TGF-β; 1 and prolactin(PRL) levels in the supernatant of MMQ cells treated with increasing doses of fulvestrant for 24 h were measured by ELISA. The Smad3 phosphorylation levels following 24 h exposure to fulvestrant in MMQ cells were detected by immunofluorescence staining. Results Fulvestrant caused significant cytotoxicity in MMQ cells with a dose- and time-dependent manner. At the same time, MMQ cells were treated with fulvestrant increased active TGF-β; 1 levels and decreased PRL levels in a dose-dependent manner. In addition, the activated Smad3 in MMQ cells was significantly increased in cell cytoplasm and nucleus (mainly in cell nucleus) after following exposure to fulvestrant. Conclusion Fulvestrant maybe inhibit the proliferation and secretion of prolactin in MMQ cells through TGF- /Smad3 signaling pathway.

Key words: fulvestrant, estrogen receptor antagonist, TGF-β/Smad3 pathway;, prolactinoma, MMQ cell

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