Li Chuzhong, Sun Zelin, Gui Songbai, Liu Fangjun, Zhang Yazhuo
Capital Medical University, Beijing, China.
Neuro Endocrinol Lett. 2009;30(2):268-74.
Unlike the successful endocrine therapy of breast cancers and other estrogen-dependent diseases, little is known about the effect of anti-estrogen treatment on pituitary tumors. Our objectives were to study the effect of fulvestrant, a new type anti-estrogen devoid of any agonistic activities, on prolactinoma cell line MMQ in vitro and its possible mechanisms.
In the experiment, the prolactin concentration, proliferation and apoptosis of the MMQ cell were measured to investigate the anti-tumor effect of the fulvestrant. The expression of estrogen receptor (ESR) mRNA and protein and MAPK pathway-related proteins ERK1 and 2, JNK, and p38 were measured to investigate the possible mechanisms.
Fulvestrant significantly inhibited prolactin secretion (up to 85.5%), decreased proliferation (IC50 = 32.4 nmol/l), and promoted apoptosis of the MMQ cells.
The suppression was possibly mediated by inhibition of ESR mRNA expression, down-regulation of ESR expression and activation of MAPK pathway-related proteins. Thus, fulvestrant has suppressive effects on prolactinoma cells and its anti-tumor mechanism appears to be related to the inhibition of ESR and the MAPK pathway.
与乳腺癌及其他雌激素依赖性疾病成功的内分泌治疗不同，关于抗雌激素治疗对垂体瘤的影响知之甚少。我们的目的是研究新型无任何激动活性的抗雌激素药物氟维司群对体外泌乳素瘤细胞系MMQ的作用及其可能机制。
在实验中，检测MMQ细胞的泌乳素浓度、增殖和凋亡情况，以研究氟维司群的抗肿瘤作用。检测雌激素受体（ESR）mRNA和蛋白以及丝裂原活化蛋白激酶（MAPK）途径相关蛋白细胞外信号调节激酶1和2（ERK1和2）、应激活化蛋白激酶（JNK）和p38的表达，以研究可能机制。
氟维司群显著抑制泌乳素分泌（高达85.5%），降低增殖（半数抑制浓度[IC50]=32.4 nmol/L），并促进MMQ细胞凋亡。
这种抑制作用可能是通过抑制ESR mRNA表达、下调ESR表达以及激活MAPK途径相关蛋白介导的。因此，氟维司群对泌乳素瘤细胞有抑制作用，其抗肿瘤机制似乎与抑制ESR和MAPK途径有关。
