Hrubá E, Pernicová Z, Pálková L, Souček K, Vondráček J, Machala M
Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v. v. i., Brno, Czech Republic.
Department of Chemistry and Toxicology, Veterinary Research Institute, Brno, Czech Republic.
Folia Biol (Praha). 2014;60 Suppl 1:56-61.
Phthalate esters are ubiquitous environmental pollutants widely used as plasticizers, which have been shown to interfere with both endocrine regulation and development of reproductive organs. In the present study, we examined the impact of diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP) on the proliferation of androgen-sensitive human prostate carcinoma LNCaP cells and related events. The results showed that both compounds were able to inhibit cell cycle progression in a dose-dependent manner. However, only DEHP was found to weakly reduce androgen receptor (AR) protein levels after long-term exposure, while only DBP partially inhibited expression of the prostate-specific antigen (KLK3) gene, a model AR transcriptional target. This indicated that inhibition of cell proliferation was likely independent of any AR modulations. Both phthalates induced suppression of cell proliferation, but none of them affected the levels of markers associated with neuroendocrine transdifferentiation (NED) in LNCaP cells. Taken together, the presented data indicate that phthalates may exert long-term negative effects on the proliferation of prostate epithelial cells derived from the carcinoma model, which are, nevertheless, largely independent of the modulation of AR expression/activity, and which do not alter further processes associated with NED.
邻苯二甲酸酯是广泛用作增塑剂的普遍存在的环境污染物，已被证明会干扰内分泌调节和生殖器官的发育。在本研究中，我们研究了邻苯二甲酸二（2-乙基己基）酯（DEHP）和邻苯二甲酸二丁酯（DBP）对雄激素敏感的人前列腺癌LNCaP细胞增殖及相关事件的影响。结果表明，这两种化合物均能以剂量依赖的方式抑制细胞周期进程。然而，仅发现长期暴露后DEHP能微弱降低雄激素受体（AR）蛋白水平，而仅DBP部分抑制前列腺特异性抗原（KLK3）基因的表达，KLK3基因是AR转录靶点的一个模型。这表明细胞增殖的抑制可能与任何AR调节无关。两种邻苯二甲酸酯均诱导细胞增殖受抑制，但它们均未影响LNCaP细胞中与神经内分泌转分化（NED）相关的标志物水平。综上所述，所呈现的数据表明，邻苯二甲酸酯可能对源自癌模型的前列腺上皮细胞增殖产生长期负面影响，然而，这种影响在很大程度上独立于AR表达/活性的调节，并且不会改变与NED相关的进一步过程。
