Curcumin suppresses breast tumor angiogenesis by abrogating osteopontin-induced VEGF expression
Curcumin suppresses breast tumor angiogenesis by abrogating osteopontin-induced VEGF expression
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DOI：
10.3892/mmr_00000005
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发表时间：
2008-09-01
影响因子：
3.4
通讯作者：
Kundu, Gopal C.
中科院分区：
文献类型：
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作者：
Chakraborty, Goutam;Jain, Shalini;Kundu, Gopal C.
恶性肿瘤的发展和进展取决于肿瘤内新血管的形成。这种现象被称为肿瘤血管生成。血管生成是癌症进展过程中发生的基本过程之一，并且取决于各种血管生成分子、细胞因子、生长因子、激酶和转录因子的表达和激活。我们最近证实，趋化因子样ECM相关蛋白骨桥蛋白（OPN）通过上调人乳腺癌模型中血管内皮生长因子（VEGF）的表达来开启血管生成开关。此外，我们提出靶向OPN诱导的VEGF表达可能是治疗乳腺癌的潜在治疗方法。在这项研究中，我们证明，姜黄素（二阿魏酰甲烷）废除OPN诱导的VEGF表达和抑制OPN诱导的VEGF依赖性乳腺肿瘤血管生成在体内。我们还探索了姜黄素与抗VEGF或抗神经纤毛蛋白（NRP）-1抗体组合与单独的姜黄素相比表现出增强的抗血管生成活性的事实。我们的研究结果表明，姜黄素抑制OPN诱导的VEGF表达和肿瘤血管生成，并建议这项研究可能有助于开发一种基于姜黄素的OPN靶向治疗方法来控制乳腺肿瘤血管生成。
The development and progression of malignant tumors depends on the formation of new blood vessels inside the tumor. This phenomenon is termed tumor angiogenesis. Angiogenesis is one of the fundamental processes that occur during cancer progression, and depends on the expression and activation of various angiogenic molecules, cytokines, growth factors, kinases and transcription factors. We recently demonstrated that the chemokine-like ECM-associated protein osteopontin (OPN) turns on the angiogenic switch by upregulating expression of vascular endothelial growth factor (VEGF) in a human breast cancer model. Furthermore, we proposed that targeting OPN-induced VEGF expression could be a potential therapeutic approach for the treatment of breast cancer. In this study, we demonstrate that curcumin (diferuloylmethane) abrogates OPN-induced VEGF expression and curbs OPN-induced VEGF-dependent breast tumor angiogenesis in vivo. We also explore the fact that curcumin in combination with anti-VEGF or anti-neuropilin (NRP)-1 antibody exhibits enhanced anti-angiogenic activity compared to curcumin alone. Our results indicate that curcumin suppresses OPN-induced VEGF expression and tumor angiogenesis, and suggest that this study may aid in the development of a curcumin-based OPN-targeted therapeutic approach to the control of breast tumor angiogenesis.