Triptolide inhibits pituitary adenoma cell viability, migration and invasion via ADAM12/EGFR signaling pathway
Triptolide inhibits pituitary adenoma cell viability, migration and invasion via ADAM12/EGFR signaling pathway
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雷公藤甲素通过 ADAM12/EGFR 信号通路抑制垂体腺瘤细胞活力、迁移和侵袭
DOI：
10.1016/j.lfs.2017.12.037
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发表时间：
2018-02
期刊：
影响因子：
6.1
通讯作者：
Lei T
中科院分区：
文献类型：
--
作者：
Wang Junwen;Zhang Zhuo;Li Ran;Sun Wei;Chen Juan;Zhang Huaqiu;Shu Kai;Lei Ting;Shu K;Lei T
雷公藤甲素（AimTriptolide）是雷公藤的一种有效成分，对多种肿瘤具有广谱的抗肿瘤活性。然而，雷公藤甲素在垂体腺瘤中的潜在作用尚不清楚。本研究旨在探讨雷公藤甲素在调节垂体腺瘤细胞活力、迁移和侵袭中的确切作用及其机制。主要方法以小鼠垂体腺瘤细胞（TtT/GF和AtT20细胞）为实验模型，用不同浓度的雷公藤甲素处理。研究了其对细胞活力、迁移、侵袭和凋亡的抑制作用，并通过研究ADAM12（一种分解素和金属蛋白酶12）/EGFR信号来确定其潜在机制。striptolide显著抑制TtT/GF和AtT20细胞的活力、迁移和侵袭，且呈剂量依赖性。在机制上，雷公藤甲素显著降低了ADAM12蛋白水平的表达，减弱了ADAM12/EGFR信号。同时，雷公藤甲素联合adam12沉默处理增强了对细胞活力、迁移和侵袭的抑制作用，adam12恢复后，这些作用得以恢复。雷公藤甲素在体内抑制TtT/GF和AtT20细胞的肿瘤发生。我们的研究证明雷公藤甲素通过ADAM12/EGFR信号通路抑制垂体腺瘤细胞的活力、迁移和侵袭。这些发现提示雷公藤甲素在治疗垂体腺瘤中的潜在作用。
AimTriptolide, an effective component derived from Tripterygium wilfordii, has been well recognized to process a broad-spectrum antitumor activities in various tumor types. However, the potential role of triptolide in pituitary adenomas remains unknown. The aim of this study was to investigate the precise role of triptolide and underlying mechanism in regulating pituitary adenoma cell viability, migration and invasion.Main methodsWe use mouse pituitary adenoma cells (TtT/GF and AtT20 cells) as the experiment model and treated them with varying concentrations of triptolide. The corresponding inhibitory effects on cell viability, migration, invasion and apoptosis were examined respectively, and the underlying mechanism was determined by investigating ADAM12 (a disintegrin and metalloprotease 12)/EGFR signaling.Key findingsTriptolide significantly inhibited cell viability, migration and invasion in TtT/GF and AtT20 cells in a dose-dependent manner. Mechanistically, triptolide significantly reduced ADAM12 expression at protein levels and attenuated ADAM12/EGFR signaling. Meanwhile, triptolide treatment combined withADAM12silencing enhanced the suppression effects on cell viability, migration and invasion, and those effects were restored following ADAM12-rescued. Moreover, triptolide suppressed the tumorigenesis of TtT/GF and AtT20 cellsin vivo.SignificanceOur research provides evidence that triptolide inhibits pituitary adenoma cell viability, migration and invasion via ADAM12/EGFR signaling pathway. These findings suggest a potential role for triptolide in treating pituitary adenomas.
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影响因子：
3.7
作者：
Kumar A;Corey C;Scott I;Shiva S;D'Cunha J
通讯作者：
D'Cunha J
低剂量雷公藤甲素通过活性氧生成和 DNA 损伤反应破坏逆转成人急性淋巴细胞白血病细胞的化疗耐药性
影响因子：
--
作者：
Zhao H;Shi P;Deng M;Jiang Z;Li Y;Kannappan V;Wang W;Li P;Xu B
通讯作者：
Xu B
影响因子：
3
作者：
Nyren-Erickson, Erin K.;Jones, Justin M.;Srivastava, D. K.;Mallik, Sanku
通讯作者：
Mallik, Sanku
DOI：
10.3390/molecules16065283
发表时间：
2011-06-23
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Liu Z;Ma L;Zhou GB
通讯作者：
Zhou GB
影响因子：
2.2
作者：
El-Sharkawy, Eman R.;Mahmoud, Khaled
通讯作者：
Mahmoud, Khaled