2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits human ovarian cancer cell proliferation.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits human ovarian cancer cell proliferation.
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2,3,7,8-四氯二苯并-对-二恶英 (TCDD) 抑制人卵巢癌细胞增殖。
DOI：
10.1007/s13402-014-0206-4
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发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Zheng J
中科院分区：
文献类型：
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作者：
Li Y;Wang K;Jiang YZ;Chang XW;Dai CF;Zheng J
芳烃受体（AhR）是一种配体激活的转录因子，介导广泛的生物学过程，包括卵巢生长和排卵。最近，我们发现内源性AhR配体（ITE）可以通过AhR抑制卵巢癌的增殖和迁移。在这里，我们测试是否2，3，7，8-四氯二苯并-p-二恶英（TCDD，一种外源性AhR配体）可以发挥类似的抗卵巢癌活性使用人类卵巢癌和非癌人类卵巢表面上皮细胞。使用两种人卵巢癌细胞系（SKOV-3和OVCAR-3）和一种人卵巢表面上皮细胞系（IOSE-385）。分别使用结晶紫和FluoroBlok插入系统测定法测定细胞增殖和迁移活性。Western blotting检测AhR蛋白表达。通过qPCR评估细胞色素P450家族1成员A1（CYP 1A 1）和成员B1（CYP 1B 1）mRNA的表达。小干扰RNA（siRNA）用于敲低AhR表达。我们发现TCDD剂量依赖性地抑制OVCAR-3细胞增殖，在100 nM时具有最大效应（约70%降低）。但TCDD对SKOV-3和IOSE-385细胞的增殖和迁移无明显影响。TCDD抑制OVCAR-3细胞增殖的IC 50估计值为4.6 nM。在10 nM时，TCDD时间依赖性地降低了SKOV-3、OVCAR-3和IOSE-385细胞中的AhR蛋白水平，同时显著增加了CYP 1A 1和CYP 1B 1 mRNA水平，表明AhR信号转导被激活。siRNA介导的AhR敲低容易阻断TCDD介导的对OVCAR-3细胞增殖的抑制。我们的数据表明，TCDD可以通过AhR信号通路抑制人卵巢癌细胞增殖，并且TCDD在至少一个人卵巢癌细胞亚群中表现出抗增殖活性。
The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, mediates a broad spectrum of biological processes, including ovarian growth and ovulation. Recently, we found that an endogenous AhR ligand (ITE) can inhibit ovarian cancer proliferation and migration via the AhR. Here, we tested whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an exogenous AhR ligand) may exert similar anti-ovarian cancer activities using human ovarian cancer and non-cancerous human ovarian surface epithelial cells. Two human ovarian cancer cell lines (SKOV-3 and OVCAR-3) and one human ovarian surface epithelial cell line (IOSE-385) were used. Cell proliferation and migration activities were determined using crystal violet and FluoroBlok insert system assays, respectively. AhR protein expression was assessed by Western blotting. Expression of cytochrome P450, family 1, member A1 (CYP1A1) and member B1 (CYP1B1) mRNA was assessed by qPCR. Small interfering RNAs (siRNAs) were used to knock down AhR expression. We found that TCDD dose-dependently suppressed OVCAR-3 cell proliferation, with a maximum effect (~70 % reduction) at 100 nM. However, TCDD did not affect SKOV-3 and IOSE-385 cell proliferation and migration. The estimated IC50 of TCDD for inhibiting OVCAR-3 cell proliferation was 4.6 nM. At 10 nM, TCDD time-dependently decreased AhR protein levels, while it significantly increased CYP1A1 and CYP1B1 mRNA levels in SKOV-3, OVCAR-3 and IOSE-385 cells, indicating activation of AhR signaling. siRNA-mediated AhR knockdown readily blocked TCDD-mediated suppression of OVCAR-3 cell proliferation. Our data indicate that TCDD can suppress human ovarian cancer cell proliferation via the AhR signaling pathway and that TCDD exhibits an anti-proliferative activity in at least a subset of human ovarian cancer cells.