Luteolin reduces the invasive potential of malignant melanoma cells by targeting β3 integrin and the epithelial-mesenchymal transition
Luteolin reduces the invasive potential of malignant melanoma cells by targeting β3 integrin and the epithelial-mesenchymal transition
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木犀草素通过靶向 β3 整合素和上皮间质转化来降低恶性黑色素瘤细胞的侵袭潜力
DOI：
10.1038/aps.2012.93
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发表时间：
2012-07
影响因子：
8.2
通讯作者：
Yin Lu
中科院分区：
文献类型：
--
作者：
Aiyun Wang;Shizhong Zheng;Shaoming Wang;Yin Lu
目的：研究木犀草素（一种高度普遍的黄酮类化合物）是否在体外和体内逆转上皮间质转化（EMT）的影响，并确定这种逆转的机制。方法：将小鼠恶性黑色素瘤B16F10细胞暴露于1% O 2 24小时。分别使用Boyden小室transwell测定和细胞粘附测定评估细胞迁移率和粘附。使用蛋白质印迹法检查 EMT 相关蛋白，例如 E-钙粘蛋白和 N-钙粘蛋白。雌性C57BL/6小鼠（6至8周龄）通过侧尾静脉注射B16F10细胞（每只小鼠1×10 6 个细胞0.2mL）。每天用木犀草素（10 或 20 mg/kg，腹膜内注射）治疗小鼠，持续 23 天。肿瘤注射后第23天，处死小鼠，采集肺，拍摄肺表面转移灶。组织切片进行免疫组化和HE染色分析。结果：缺氧使B16F10细胞体外形态由鹅卵石样变为间质样条带，同时细胞粘附和侵袭能力增强。木犀草素 (5− 50 μmol/L) 以剂量依赖性方式抑制缺氧引起的细胞变化。缺氧使细胞中E-cadherin的表达显着降低，而N-cadherin的表达增加（表明发生了EMT样转化），木犀草素（5 μmol/L）可逆转这种情况。在 B16F10 细胞中，木犀草素至少部分通过抑制 β3 整合素/FAK 信号通路上调 E-钙粘蛋白。在实验性转移模型小鼠中，用木犀草素（10 或 20 mg/kg）治疗可使肺部转移定植减少 50%。此外，该治疗还增加了肿瘤组织中E-cadherin的表达，同时降低了波形蛋白和β3整合素的表达。结论：木犀草素通过调节β3整合素在体外和体内抑制缺氧诱导的恶性黑色素瘤细胞的EMT，提示木犀草素可能作为潜在的抗癌化学预防和化疗药物。
Aim:To investigate whether luteolin, a highly prevalent flavonoid, reverses the effects of epithelial-mesenchymal transition (EMT) in vitro and in vivo and to determine the mechanisms underlying this reversal.Methods:Murine malignant melanoma B16F10 cells were exposed to 1% O 2 for 24 h. Cellular mobility and adhesion were assessed using Boyden chamber transwell assay and cell adhesion assay, respectively. EMT-related proteins, such as E-cadherin and N-cadherin, were examined using Western blotting. Female C57BL/6 mice (6 to 8 weeks old) were injected with B16F10 cells (1× 10 6 cells in 0.2 mL per mouse) via the lateral tail vein. The mice were treated with luteolin (10 or 20 mg/kg, ip) daily for 23 d. On the 23rd day after tumor injection, the mice were sacrificed, and the lungs were collected, and metastatic foci in the lung surfaces were photographed. Tissue sections were analyzed with immunohistochemistry and HE staining.Results:Hypoxia changed the morphology of B16F10 cells in vitro from the cobblestone-like to mesenchymal-like strips, which was accompanied by increased cellular adhesion and invasion. Luteolin (5− 50 μmol/L) suppressed the hypoxia-induced changes in the cells in a dose-dependent manner. Hypoxia significantly decreased the expression of E-cadherin while increased the expression of N-cadherin in the cells (indicating the occurrence of EMT-like transformation), which was reversed by luteolin (5 μmol/L). In B16F10 cells, luteolin up-regulated E-cadherin at least partly via inhibiting the β3 integrin/FAK signal pathway. In experimental metastasis model mice, treatment with luteolin (10 or 20 mg/kg) reduced metastatic colonization in the lungs by 50%. Furthermore, the treatment increased the expression of E-cadherin while reduced the expression of vimentin and β3 integrin in the tumor tissues.Conclusion:Luteolin inhibits the hypoxia-induced EMT in malignant melanoma cells both in vitro and in vivo via the regulation of β3 integrin, suggesting that luteolin may be applied as a potential anticancer chemopreventative and chemotherapeutic agent.
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影响因子：
13.7
作者：
Virgili, Gianni;Gatta, Gemma;Paci, Eugenio
通讯作者：
Paci, Eugenio
影响因子：
11.2
作者：
Alonso, Soledad R.;Tracey, Lorraine;Rodriguez-Peralto, Jose L.
通讯作者：
Rodriguez-Peralto, Jose L.
DOI：
10.1186/bcr2938
发表时间：
2012-01-19
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dave B;Mittal V;Tan NM;Chang JC
通讯作者：
Chang JC
影响因子：
1.5
作者：
Berk, David R.;LaBuz, Elizabeth;Swetter, Susan M.
通讯作者：
Swetter, Susan M.
影响因子：
11.2
作者：
Byun, Sanguine;Lee, Ki Won;Dong, Zigang
通讯作者：
Dong, Zigang