Emodin inhibits invasion and migration of prostate and lung cancer cells by downregulating the expression of chemokine receptor CXCR4
Emodin inhibits invasion and migration of prostate and lung cancer cells by downregulating the expression of chemokine receptor CXCR4
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DOI：
10.3109/08923973.2012.654494
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发表时间：
2012-10-01
影响因子：
3.3
通讯作者：
Ahn, Kwang Seok
中科院分区：
文献类型：
--
作者：
Ok, Sooho;Kim, Sung-Moo;Ahn, Kwang Seok
大黄素（艾德）是一种蒽醌衍生物，具有抑制细胞增殖、诱导细胞凋亡、抑制血管生成、抑制肿瘤转移和增强化疗作用。然而，艾德与调节CXC趋化因子受体4（CXCR 4）基因表达相关的详细机制尚未完全了解，CXCR 4基因表达影响前列腺癌和肺癌细胞的细胞迁移和侵袭。最近的证据表明，CXCR 4/CXCL 12轴参与促进肿瘤的侵袭和转移。因此，可以下调CXCR 4表达的新药物在抑制癌症转移方面具有治疗潜力。在艾德及其衍生物中，发现艾德下调CXCR 4和HER 2的表达，而不影响肿瘤细胞中的细胞活力。发现艾德对CXCR 4表达的抑制与抑制CXCL 12诱导的DU 145和A549细胞的迁移和侵袭相关。此外，无论是蛋白酶体抑制或溶酶体的稳定性有任何影响ED诱导的CXCR 4表达的减少。其基本分子机制揭示了CXCR 4在转录水平的下调，表现为下调mRNA表达和抑制NF-κ B B的活化。总的来说，我们的研究结果表明，艾德是一种新的CXCR 4表达阻滞剂，因此，作为一种强大的治疗转移性癌症的药物具有巨大的潜力。
Emodin (ED), an anthraquinone derivative, has been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, impede metastasis, and enhance chemotherapy. However, the detailed mechanism of ED related to the regulation of CXC chemokine receptor-4 (CXCR4) gene expression that affects cellular migration and invasion in prostate and lung cancer cells are not fully understood. Recent evidence indicates that the CXCR4/CXCL12 axis is involved in promoting invasion and metastasis in tumors. Thus, novel agents that can downregulate CXCR4 expression have therapeutic potential in repressing cancer metastasis. Among ED and its derivatives, it is found that ED downregulated the expression of both CXCR4 and HER2 without affecting cell viability in tumor cells. The suppression of CXCR4 expression by ED was found to correlate with the inhibition of CXCL12-induced migration and invasion of both DU145 and A549 cells. Besides, neither proteasome inhibition nor lysosomal stabilization had any effect on ED-induced decrease in CXCR4 expression. The basic molecular mechanisms unveiled that the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression and suppression of NF-kappa B activation. Overall, our findings suggest that ED is a novel blocker of CXCR4 expression and, thus, has enormous potential as a powerful therapeutic agent for metastatic cancer.