Di-(2-ethylhexyl) phthalate suppresses tamoxifen-induced apoptosis in GH3 pituitary cells
Di-(2-ethylhexyl) phthalate suppresses tamoxifen-induced apoptosis in GH3 pituitary cells
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DOI：
10.1007/s00204-006-0132-y
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发表时间：
2006
影响因子：
6.1
通讯作者：
H. Kim;M. Ishizaka;A. Kazusaka;S. Fujita
中科院分区：
文献类型：
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作者：
H. Kim;M. Ishizaka;A. Kazusaka;S. Fujita
雌激素受体拮抗剂三苯氧胺（Tamoxifen）是一种临床上常用的抗肿瘤药物，可诱导垂体细胞GH 3凋亡。虽然邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种众所周知的环境雌激素，并且预期会暴露于该化学品，但关于DEHP对他莫昔芬诱导的垂体细胞凋亡的影响的报告有限。在细胞毒性试验中，DEHP（250 μM）处理4天可逆转他莫昔芬处理的GH 3细胞中细胞活力降低。为了表征细胞死亡，使用Hoechst 33258对细胞进行染色。DEHP处理可抑制三苯氧胺诱导的细胞凋亡形态学改变，如染色质浓缩。流式细胞仪分析显示，DEHP处理显著减少了他莫昔芬诱导的凋亡细胞数量。DEHP也抑制了他莫昔芬处理增强的聚（ADP-核糖）聚合酶（PARP）裂解。这些结果表明，DEHP抑制他莫昔芬诱导的细胞凋亡与其在GH 3细胞中的雌激素效应相关，并可能抵消他莫昔芬的治疗作用。
Tamoxifen, an estrogen receptor antagonist, has been clinically used as an antitumor drug and induces apoptosis in GH3 pituitary cells. Although di-(2-ethylhexyl) phthalate (DEHP) is a well-known environmental estrogen and the exposure to this chemical is well expected, reports are limited regarding effects of DEHP on tamoxifen-induced apoptosis in pituitary cells. In the cytotoxicity assay, the reduced cell viability in tamoxifen-treated GH3 cells was reversed by DEHP (250 μM) treatment for 4 days. To characterize cell death, cells were stained using Hoechst 33258. Apoptotic morphological change such as chromatin condensation induced by tamoxifen was suppressed by treatment with DEHP. Flow cytometric analysis revealed that the number of apoptotic cells induced by tamoxifen was significantly decreased by DEHP treatment. Enhanced poly (ADP-ribose) polymerase (PARP) cleavage by tamoxifen treatment was also inhibited by DEHP. These results suggest that DEHP suppresses tamoxifen-induced apoptosis in association with its estrogenic effect in GH3 cells and might counteract the therapeutic effect of tamoxifen.