Curcumin suppresses the paclitaxel-induced nuclear factor-κB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice
Curcumin suppresses the paclitaxel-induced nuclear factor-κB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice
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DOI：
10.1158/1078-0432.ccr-05-1192
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发表时间：
2005-10-15
影响因子：
11.5
通讯作者：
Price, JE
中科院分区：
文献类型：
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作者：
Aggarwal, BB;Shishodia, S;Price, JE
目前，在针对原发性肿瘤使用手术、放射和化学疗法之后，对于转移性乳腺癌没有有效的疗法。由于姜黄素抑制核因子-κ B（NF-κ B）活化，并且大多数化疗药物激活NF-κ B，其介导细胞存活、增殖、侵袭和转移，因此我们假设姜黄素将增强化疗在晚期乳腺癌中的作用并抑制肺转移。我们使用紫杉醇耐药乳腺癌细胞和人乳腺癌异种移植模型来验证这一假设。如电泳迁移率凝胶位移试验所示，紫杉醇激活乳腺癌细胞中的NF-κ B，姜黄素抑制NF-κ B;这种抑制作用是通过抑制I κ B α激酶激活和I κ B α磷酸化和降解介导的。姜黄素还抑制紫杉醇诱导的抗凋亡蛋白（XIAP、IAP-1、IAP-2、Bcl-2和Bcl-xL）、增殖蛋白（环氧合酶2、c-Myc和细胞周期蛋白D1）和转移蛋白（血管内皮生长因子、基质金属蛋白酶-9和细胞间粘附分子-1）的表达。它还增强了细胞凋亡。在人乳腺癌异种移植模型中，饮食给予姜黄素显著降低了乳腺癌肺转移的发生率，并抑制了NF-κ B、环氧合酶2和基质金属蛋白酶9的表达。总的来说，我们的研究结果表明，姜黄素，这是一种安全的化合物，有可能通过抑制NF-κ B B和NF-κ B调节的基因产物，在预防乳腺癌转移的治疗潜力。
Currently, there is no effective therapy for metastatic breast cancer after surgery, radiation, and chemotherapy have been used against the primary tumor. Because curcumin suppresses nuclear factor-kappa B (NF-kappa B) activation and most chemotherapeutic agents activate NF-kappa B that mediates cell survival, proliferation, invasion, and metastasis, we hypothesized that curcumin would potentiate the effect of chemotherapy in advanced breast cancer and inhibit lung metastasis. We tested this hypothesis using paclitaxel (Taxol)-resistant breast cancer cells and a human breast cancer xenograft model. As examined by electrophoretic mobility gel shift assay, paclitaxel activated NF-kappa B in breast cancer cells and curcumin inhibited it; this inhibition was mediated through inhibition of I kappa B alpha kinase activation and I kappa B alpha phosphorylation and degradation. Curcumin also suppressed the paclitaxel-induced expression of antiapoptotic (XIAP, IAP-1, IAP-2, Bcl-2, and Bcl-xL), proliferative (cyclooxygenase 2, c-Myc, and cyclin D1), and metastatic proteins (vascular endothelial growth factor, matrix metalloproteinase-9, and intercellular adhesion molecule-1). It also enhanced apoptosis. In a human breast cancer xenograft model, dietary administration of curcumin significantly decreased the incidence of breast cancer metastasis to the lung and suppressed the expression of NF-kappa B, cyclooxygenase 2, and matrix metalloproteinase-9. Overall, our results indicate that curcumin, which is a pharmacologically safe compound, has a therapeutic potential in preventing breast cancer metastasis possibly through suppression of NF-kappa B and NF-kappa B-regulated gene products.