Concentration-dependent effects of a selective estrogen receptor modulator raloxifene on proliferation and apoptosis in human uterine leiomyoma cells cultured in vitro
Concentration-dependent effects of a selective estrogen receptor modulator raloxifene on proliferation and apoptosis in human uterine leiomyoma cells cultured in vitro
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DOI：
10.1093/humrep/del515
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发表时间：
2007-05-01
影响因子：
6.1
通讯作者：
Maruo, Takeshi
中科院分区：
文献类型：
--
作者：
Liu, Jin;Matsuo, Hiroya;Maruo, Takeshi
背景：本研究旨在探讨雷洛昔芬对体外培养的人子宫肌瘤细胞增殖和凋亡的影响。方法：用不同浓度（10（-9）M、10（-8）M和10（-7）M）的雷洛昔芬和10（-7）M 17 β-雌二醇（E-2）处理单层培养物。采用3-HT法检测细胞存活率、增殖细胞核抗原（PCNA）阳性细胞百分率、末端脱氧核苷酸转移酶介导的5 '-三磷酸脱氧尿苷缺口末端标记（TUNEL）阳性细胞百分率以及PCNA和Bcl-2蛋白表达。（4，5-二甲基噻唑-2-基）-5-（3-羧基甲基苯基）-2-（4-磺基苯基）-2H-四唑测定、免疫细胞化学、TUNEL测定和western印迹分析。研究结果：与未处理的培养物相比，用10（-9）M雷洛昔芬处理的培养物的活细胞数、PCNA阳性细胞百分比和PCNA蛋白表达显著降低，但用10（-8）M或10（-7）M雷洛昔芬处理的培养物的活细胞数、PCNA阳性细胞百分比和PCNA蛋白表达增加。相反，用10（-9）M雷洛昔芬处理后，TUNEL阳性细胞的百分比显著增加，Bcl-2蛋白表达显著降低，而用10（-8）或10（-7）M雷洛昔芬处理后，它们不受影响。结论：在培养的平滑肌瘤细胞中，低浓度（10（-9）M）的雷洛昔芬可能抑制平滑肌瘤细胞的生长，而高浓度（10（-8）M，10（-7）M）的雷洛昔芬可能促进其生长。
BACKGROUND: This study was conducted to elucidate the effects of raloxifene on proliferation and apoptosis in cultured human uterine leiomyoma cells. METHODS: The monolayer cultures were treated with graded concentrations (10(-9),10(-8) and 10(-7) M) of raloxifene and 10(-7) M 17 beta-estradiol (E-2). Cell viability, percentage of proliferating cell nuclear antigen (PCNA)-positive cells, percentage of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labelling (TUNEL)-positive cells and the expression of PCNA and Bcl-2 proteins were assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxylphenyl)-2-(4-sulphophenyl)-2H-tetraz olium assay, immunocytochemistry, TUNEL assay and western blot analysis, respectively. RESULTS: Compared with untreated cultures, the number of viable cultured cells, percentage of PCNA-positive cells and PCNA protein expression were significantly decreased by treatment with 10(-9) M raloxifene, but increased by treatment with either 10(-8) M or 10(-7) M raloxifene. In contrast, the percentage of TUNEL-positive cells was significantly increased and Bcl-2 protein expression was significantly decreased by treatment with 10(-9) M raloxifene, whereas they were not affected by treatment with either 10(-8) or 10(-7) M raloxifene. CONCLUSIONS: In cultured leiomyoma cells, low concentration (10(-9) M) of raloxifene may inhibit the growth of leiomyoma cells, whereas high concentrations (10(-8) M, 10(-7) M) of raloxifene may promote their growth.