氟维司群对泌乳素瘤GH3细胞系增殖和分泌的影响

目的探讨雌激素受体拮抗剂氟维司群对泌乳素腺瘤GH3细胞增殖和分泌泌乳素的影响。方法将GH3细胞分为对照组、不同浓度的氟维司群组（0．04、1、25、625nM）和雌二醇组。观察氟维司群和雌二醇对GH3细胞活力、泌乳素水平、凋亡以及转化生长因子-β3（Transforming growth factorβ3，TGF—β3）的影响。结果与对照组相比，雌二醇组GH3细胞活力明显增加（P〈0．01），氟维司群25nM组和625nM组细胞活力分别下降35．3％和42．4％，差异显著（P〈0．01）。与对照组和雌二醇组相比，1nM组凋亡细胞增加，差异有统计学意义（P〈0．05），25nM组和625nM组凋亡细胞数分别占总细胞数12．9％和17．3％．差异显著（P〈0．01）。与对照组相比，氟维司群能抑制泌乳素分泌，25nM组和625nM组分别下降62.3％和81．6％，差异佩著（P〈0．01）。蛋白印迹试验证实雌激素可抑制TGF—β3表达，随着氟维司群浓度增加，TGF-β3表达量逐渐上升。结论雌二醇可促进GH3细胞增殖和泌乳素分泌，而雌激素受体拮抗剂氟维司群能够有效抑制雌激素作用，期问有TGF—β3参与，为泌乳素瘤临床治疗提供新的药物选择。

Effects of fulvestrant on proliferation and secretion of prolactinoma GH3 cells

Objective To investigate effects of fulvestrant on the proliferation, secretion of prolactin and apoptosis of prolactinoma GH3 cells. Methods The prolactinoma GH3 cells were divided into control group, fulvestrant group （0.04,1,25,625 nM） and estradiol group. Fulvestrant （0.04, 1, 25,625 nM） and estradiol were added respectively at different concentrations into the culture medium. The cell viability of prolactinoma GH3 cells, prolactin levels, apoptosis and transforming growth factor-β3 （TGF-β3） were determined. Results Compared with the control group, cell viability was increased after estradiol exposure （P 〈 0.01）, and reduced by 35.3% and 42.4% respectively in 25 nM and 625 nM fulvestrant group （P 〈 0.01）. Compared with the control group and the estradiol group, apoptosis cell was increased in 1 nM fulvestrant group （P 〈 0.05）, and increased to 12.9% and 17.3% in 25 nM and 625 nM fulvestrant group respectively （P 〈 0.01）. Compared with the control group, prolactin level was inhibited more significantly by fulvestrant. The prolactin was decreased by 62.3% and 81.6% respectively in 25 nM and 625 nM group with a significant difference （P 〈 0.01）. And TGF-β3 protein level was down-regulated after estradiol exposure and up-regulated after fulvestrant exposure in a dose-dependent manner. Conclusions The proliferation of prolactinoma GH3 cells and the secretion of prolactin may be promoted by estradiol, but estrogen receptor antagonist, fulvestrant, can effectively inhibit the promotive effects of estradiol on proliferation of prolactinoma GH3 cells and secretion of prolactin, and TGF-β3 involved the phenomena, thus indicating that fulvestrant would be a potential d~ug for prolactinoma.