Cucurbitacin E inhibits breast tumor metastasis by suppressing cell migration and invasion
Cucurbitacin E inhibits breast tumor metastasis by suppressing cell migration and invasion
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葫芦素 E 通过抑制细胞迁移和侵袭抑制乳腺肿瘤转移
DOI：
10.1007/s10549-012-2175-5
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发表时间：
2012-09-01
影响因子：
3.8
通讯作者：
Yi, Zhengfang
中科院分区：
文献类型：
--
作者：
Zhang, Tao;Li, Jingjie;Yi, Zhengfang
肿瘤转移是肿瘤患者死亡的主要原因。乳腺癌是一种高度恶性的肿瘤，具有很大的转移潜能，因此有必要开发新的潜在药物来预防肿瘤转移。在这里，我们报告了我们的发现与葫芦素E（CuE，α-elaterin），四环三萜化合物从葫芦科分离。在体内和体外评估CuE对乳腺癌转移抑制的效力。在我们的动物实验中，腹腔注射CuE显着抑制乳腺肿瘤转移到肺，而不影响接种的4 T1和MDA-MB-231乳腺癌细胞的凋亡或增殖。用CuE处理转移性乳腺肿瘤细胞在体外显著阻断肿瘤细胞的迁移和侵袭。随后的研究表明，CuE可抑制Arp 2/3依赖的肌动蛋白聚合，并抑制Src/FAK/Rac 1/MMP参与的信号通路。总体而言，我们的数据表明，CuE通过抑制肿瘤细胞迁移和侵袭来阻断乳腺癌转移。我们提供了第一个证据的一个新的作用，CuE作为一个潜在的候选人治疗乳腺癌转移。
Tumor metastasis is the main cause of cancer-related deaths of patients. Breast cancer is highly malignant with considerable metastatic potential, which urges the necessity for developing novel potential drug candidate to prevent tumor metastasis. Here, we report our finding with Cucurbitacin E (CuE, α-elaterin), a tetracyclic triterpenes compound isolated from Cucurbitaceae. The potency of CuE on breast cancer metastasis inhibition was assessed in vivo and in vitro. In our animal experiments, intraperitoneal administrations of CuE significantly inhibited breast tumor metastasis to the lung without affecting apoptosis or proliferation of inoculated 4T1 and MDA-MB-231 breast cancer cells. Treatment of metastatic breast tumor cells with CuE markedly blocked tumor cell migration and invasion in vitro. Subsequent studies showed that CuE impaired Arp2/3-dependent actin polymerization and suppressed Src/FAK/Rac1/MMP involved pathway. Overall, our data demonstrate that CuE blocks breast cancer metastasis by suppressing tumor cell migration and invasion. We provide first evidence of a novel role for CuE as a potential candidate for treating breast cancer metastasis.