Eupolyphaga sinensis Walker Ethanol Extract Suppresses Cell Growth and Invasion in Human Breast Cancer Cells
Eupolyphaga sinensis Walker Ethanol Extract Suppresses Cell Growth and Invasion in Human Breast Cancer Cells
复制标题
土鳖虫乙醇提取物抑制人乳腺癌细胞的生长和侵袭
DOI：
10.1177/1534735415598224
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发表时间：
2016-03-01
影响因子：
2.9
通讯作者：
Zhang, Yanmin
中科院分区：
文献类型：
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作者：
Zhan, Yingzhuan;Zhang, Han;Zhang, Yanmin
本研究的目的。目的：研究地龙70%乙醇提取物(EsWE)对乳腺癌细胞的抗增殖和抗侵袭作用，并探讨其信号转导机制。方法：研究方法。采用四甲基偶氮唑盐比色法和集落形成实验观察Eswe对乳腺癌细胞体外增殖的影响。采用小鼠移植瘤模型，观察Eswe对乳腺癌的体内治疗作用。为了探讨其可能的分子机制，我们用免疫印迹法检测了Eswe对ERK1/2、CXCR4、基质金属蛋白酶2(MMP2)和MMP9表达的影响。采用创面愈合实验和基质细胞侵袭小室实验检测基质细胞衍生因子-1α诱导的乳腺癌细胞迁移和侵袭能力。结果。ESME有效地抑制了MDA-MB-435s和MDA-MB-231细胞的增殖，并在MDA-MB-231异种移植模型中显示出抗肿瘤作用。此外，Eswe还抑制了MAPK信号转导关键分子ERK1/2的活性。我们还观察到，Eswe治疗导致CXCR4表达下调，MMP2和MMP9显著减少。ESRE通过调节自分泌血管内皮生长因子影响CXCR4的表达。然而，CXCR4表达的抑制是mRNA表达下调的结果。ESRE抑制CXCR4的表达进一步与抑制SDF-1α诱导的乳腺癌细胞迁移和侵袭有关。结论。Eswe通过调节MAPK信号转导及相关转移因子发挥抗增殖和抗侵袭作用，有望成为乳腺癌干预治疗的候选靶点。
Aim of the study. To examine the antiproliferation and anti-invasion of Eupolyphaga sinensis Walker 70% ethanol extract (ESWE) on breast cancer and elucidate the underlying signaling mechanisms. Methods. MTT and colony formation assays were used to investigate the effect of ESWE on proliferation of breast cancer cells in vitro. The xenograft mouse tumor model was used to determine the effect of ESWE on breast cancer in vivo. To investigate the underlying molecular mechanisms, we used western blotting to analyze the expression of ERK1/2, CXCR4, matrix metalloproteinase 2 (MMP2), and MMP9 pretreated with ESWE. The stromal cell–derived factor (SDF)-1α-induced migration and invasion potential of breast cancer cells were examined by wound-healing assays and Matrigel invasion chamber assays. Results. ESWE effectively inhibited the proliferation of MDA-MB-435s and MDA-MB-231 cells and exhibited antitumor effects in an MDA-MB-231 xenograft mice model. Furthermore, ESWE suppressed the activity of ERK1/2, a key molecule of MAPK signaling. We also observed that ESWE treatment led to downregulation of CXCR4 expression as well as greatly reduced MMP2 and MMP9. ESWE affected CXCR4 expression partially through the modulation of autocrine vascular endothelial growth factor. However, suppression of CXCR4 expression was the result of downregulation of mRNA expression. Inhibition of CXCR4 expression by ESWE further correlated with the suppression of SDF-1α-induced migration and invasion in breast cancer cells. Conclusion. ESWE exerted its antiproliferation and antiinvasion by regulating MAPK signaling and related metastasis factorsand thus could be a useful therapeutic candidate for breast cancer intervention.