雌激素受体β激动剂对卵巢癌细胞增殖和基因表达的影响。
Effect of estrogen receptor β agonists on proliferation and gene expression of ovarian cancer cells.
机构信息
Department of Obstetrics and Gynecology, University Medical Center Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany.
Center of Excellence for Fluorescent Bioanalytics (KFB), Am BioPark 9, 93053, Regensburg, Germany.
出版信息
BMC Cancer. 2017 May 8;17(1):319. doi: 10.1186/s12885-017-3246-0.
BACKGROUND
Estrogen receptor (ER) β has been suggested to affect ovarian carcinogenesis. We examined the effects of four ERβ agonists on proliferation and gene expression of two ovarian cancer cell lines.
METHODS
OVCAR-3 and OAW-42 ovarian cancer cells were treated with the ERβ agonists ERB-041, WAY200070, Liquiritigenin and 3β-Adiol and cell growth was measured by means of the Cell Titer Blue Assay (Promega). ERβ expression was knocked down by transfection with specific siRNA. Additionally, transcriptome analyses were performed by means of Affymetrix GeneChip arrays. To confirm the results of DNA microarray analysis, Western blot experiments were performed.
RESULTS
All ERβ agonists tested significantly decreased proliferation of OVCAR-3 and OAW-42 cells at a concentration of 10 nM. Maximum antiproliferative effects were induced by flavonoid Liquiritigenin, which inhibited growth of OVCAR-3 cells by 31.2% after 5 days of treatment, and ERB-041 suppressing proliferation of the same cell line by 29.1%. In OAW-42 cells, maximum effects were observed after treatment with the ERβ agonist WAY200070, inhibiting cell growth by 26.8%, whereas ERB-041 decreased proliferation by 24.4%. In turn, knockdown of ERβ with specific siRNA increased cell growth of OAW-42 cells about 1.9-fold. Transcriptome analyses revealed a set of genes regulated by ERβ agonists including ND6, LCN1 and PTCH2, providing possible molecular mechanisms underlying the observed antiproliferative effects.
CONCLUSION
In conclusion, the observed growth-inhibitory effects of all ERβ agonists on ovarian cancer cell lines in vitro encourage further studies to test their possible use in the clinical setting.
背景
雌激素受体（ER）β被认为会影响卵巢癌的发生。我们研究了四种 ERβ 激动剂对两种卵巢癌细胞系增殖和基因表达的影响。
方法
用 ERβ 激动剂 ERB-041、WAY200070、甘草查尔酮和 3β-二醇处理 OVCAR-3 和 OAW-42 卵巢癌细胞，并通过 Cell Titer Blue 测定法（Promega）测量细胞生长。通过转染特异性 siRNA 敲低 ERβ 表达。此外，通过 Affymetrix GeneChip 阵列进行转录组分析。为了验证 DNA 微阵列分析的结果，进行了 Western blot 实验。
结果
测试的所有 ERβ 激动剂在 10 nM 浓度下均显著降低 OVCAR-3 和 OAW-42 细胞的增殖。黄酮类甘草查尔酮诱导最大的抗增殖作用，在 5 天的治疗后，OVCAR-3 细胞的生长抑制率为 31.2%，而 ERB-041 抑制同一细胞系的增殖率为 29.1%。在 OAW-42 细胞中，用 ERβ 激动剂 WAY200070 治疗观察到最大作用，抑制细胞生长 26.8%，而 ERB-041 使增殖减少 24.4%。相反，用特异性 siRNA 敲低 ERβ 使 OAW-42 细胞的生长增加约 1.9 倍。转录组分析揭示了一组受 ERβ 激动剂调节的基因，包括 ND6、LCN1 和 PTCH2，为观察到的抗增殖作用提供了可能的分子机制。
结论
总之，所有 ERβ 激动剂在体外对卵巢癌细胞系的生长抑制作用鼓励进一步研究以测试它们在临床环境中的可能用途。
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