Department of Nutrition, The Second School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Department of Nutrition and Food Safety, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Department of Nutrition and Food Safety, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Toxicol In Vitro. 2019 Feb;54:82-88. doi: 10.1016/j.tiv.2018.09.007. Epub 2018 Sep 19.
Prostate cancer is the most common malignancy in men. Phthalate esters are a class of environmental endocrine disruptors and were reported to be cancer promoting agents, however the potential role of phthalate esters in prostate cancer has been rarely reported. Mounting evidence has shown that miR-34a is a master tumor suppressor miRNA in cancer. The aim of this study was to investigate the role of butyl benzyl phthalate (BBP), one of the typical phthalate esters, in cell proliferation of prostate cancer cells. Human prostate cancer LNCaP and PC-3 cells were exposed to low dose of BBP for 6 days. The results showed that 10 and 10 mol/L BBP increased the expression of cyclinD1 and PCNA, decreased p21 expression, and induced cell growth in both LNCaP and PC-3 cells. Furthermore, we found that BBP significantly downregulated the expression of miR-34a, along with upregulation of miR-34a target gene c-myc. Using cell tranfection of miR-34a mimic and inhibitor, we demonstrated that BBP promoted cell proliferation through miR-34a/c-myc axis in prostate cancer cells. Findings from this study could provide new insight into the involvement and the molecular mechanism of phthalate esters on prostate cancer.
前列腺癌是男性最常见的恶性肿瘤。邻苯二甲酸酯是一类环境内分泌干扰物，被报道为致癌促进剂，但邻苯二甲酸酯在前列腺癌中的潜在作用鲜有报道。越来越多的证据表明，miR-34a 是癌症中的主要肿瘤抑制 miRNA。本研究旨在探讨邻苯二甲酸丁基苄基酯（BBP）作为典型的邻苯二甲酸酯之一在前列腺癌细胞增殖中的作用。人类前列腺癌细胞 LNCaP 和 PC-3 细胞分别用低剂量的 BBP 处理 6 天。结果表明，10 和 10mol/L 的 BBP 增加了 cyclinD1 和 PCNA 的表达，降低了 p21 的表达，并诱导了 LNCaP 和 PC-3 细胞的生长。此外，我们发现 BBP 显著下调了 miR-34a 的表达，同时上调了 miR-34a 的靶基因 c-myc。通过转染 miR-34a 模拟物和抑制剂，我们证明 BBP 通过 miR-34a/c-myc 轴促进前列腺癌细胞的增殖。本研究的结果可为邻苯二甲酸酯对前列腺癌的作用及其分子机制提供新的见解。
