Bromocriptine and cabergoline induce cell death in prolactinoma cells via the ERK/EGR1 and AKT/mTOR pathway respectively
Bromocriptine and cabergoline induce cell death in prolactinoma cells via the ERK/EGR1 and AKT/mTOR pathway respectively
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溴隐亭和卡麦角林分别通过 ERK/EGR1 和 AKT/mTOR 途径诱导催乳素瘤细胞死亡
DOI：
10.1038/s41419-019-1526-0
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发表时间：
2019-04-18
影响因子：
9
通讯作者：
Ma, Chiyuan
中科院分区：
文献类型：
--
作者：
Tang, Chao;Sun, Ruixin;Ma, Chiyuan
高泌乳素血症的治疗基于多巴胺激动剂的使用，主要是溴隐亭（BRC）和卡麦角林（CAB）。它们有效地减小肿瘤大小并恢复性腺功能。然而，在泌乳素瘤患者中，CAB和BRC之间的药物敏感性存在差异，尽管其潜在机制仍不清楚。因此，我们研究了是否有差异的肿瘤敏感性CAB和BRC和他们可能的差异机制在两个泌乳素瘤细胞系。在我们的研究中，我们发现GH 3细胞对BRC更敏感，MMQ细胞对CAB更敏感。此外，BRC和CAB通过不同的途径引起细胞死亡; BRC主要通过凋亡途径诱导催乳素瘤细胞死亡，CAB主要通过自噬细胞死亡途径诱导垂体催乳素瘤细胞死亡。使用基因微阵列分析，我们发现BRC通过ERK/EGR 1信号通路诱导催乳素瘤细胞凋亡，而CAB通过抑制AKT/mTOR信号通路诱导自噬死亡。我们的研究显示了BRC和CAB处理催乳素瘤细胞的肿瘤敏感性和差异机制的差异，这为准确治疗催乳素瘤提供了理论依据。
The treatment of hyperprolactinemia is based on the use of dopamine agonists, mainly bromocriptine (BRC) and cabergoline (CAB). They reduce tumour size effectively and restore gonadal function. However, there is a difference in drug sensitivity between CAB and BRC in patients with prolactinoma, although the underlying mechanisms are still unknown. Thus, we investigated whether there are differences in tumour sensitivity to CAB and BRC and their possible differential mechanisms in two prolactinoma cell lines. In our study, we found that GH3 cells are more sensitive to BRC and that MMQ cells are more sensitive to CAB. Moreover, BRC and CAB elicited cell death via different pathways; BRC induced prolactinoma cell death mainly through the apoptosis pathway, and CAB induced pituitary prolactinoma cell death mainly via the autophagic cell death pathway. Using gene microarray analysis, we found that BRC induces the apoptosis of prolactinoma cells through the ERK/EGR1 signalling pathway, whereas CAB induces autophagic death by inhibiting the AKT/mTOR signalling pathway. Our study showed the difference in tumour sensitivity and differential mechanisms in BRC- and CAB-treated prolactinoma cells, which provides a theoretical basis for the accurate treatment of prolactinoma.