Ligustrazine inhibits B16F10 melanoma metastasis and suppresses angiogenesis induced by Vascular Endothelial Growth Factor

Angiogenesis is crucial for tumor metastasis, with many compounds that inhibit tumor metastasis acting through suppression of angiogenesis. We investigated anti-angiogenic properties of Ligustrazine in a series of in vitro and in vivo models. Ligustrazine inhibited VEGF-induced HUVECs migration and...

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Published in	Biochemical and biophysical research communications Vol. 386; no. 2; pp. 374 - 379
Main Authors	Chen, Lei, Lu, Yin, Wu, Jia-ming, Xu, Bo, Zhang, Li-juan, Gao, Ming, Zheng, Shi-zhong, Wang, Ai-yun, Zhang, Chang-bin, Zhang, Wei-wei, Lei, Na
Format	Journal Article
Language	English
Published	United States Elsevier Inc 21.08.2009
Subjects	Angiogenesis Angiogenesis Inhibitors - pharmacology Angiogenesis Inhibitors - therapeutic use Animals Cell Movement - drug effects Cell Proliferation - drug effects Female Fibroblasts - drug effects Humans Ligustrazine Lung Neoplasms - prevention & control Lung Neoplasms - secondary Melanoma, Experimental - blood supply Melanoma, Experimental - drug therapy Melanoma, Experimental - pathology Mice Mice, Inbred C57BL Microvessels - drug effects Neovascularization, Pathologic - chemically induced Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - pathology Pyrazines - pharmacology Pyrazines - therapeutic use Rats Tumor metastasis Vascular Endothelial Growth Factor A - pharmacology VEGF Ligustrazine Angiogenesis VEGF Tumor metastasis
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Abstract	Angiogenesis is crucial for tumor metastasis, with many compounds that inhibit tumor metastasis acting through suppression of angiogenesis. We investigated anti-angiogenic properties of Ligustrazine in a series of in vitro and in vivo models. Ligustrazine inhibited VEGF-induced HUVECs migration and tube formation in a dose-dependent manner in vitro, and had limited cytotoxicity to HUVECs and normal fibroblasts even at a dose up to 100 μg/ml. Ligustrazine also suppressed VEGF-induced rat aortic ring sprouting dose-dependently. In vivo, Ligustrazine reduced the Hb content in a Matrigel plug implanted in mice and inhibited new vessel formation in CAM. In addition, in a B16F10 spontaneous metastasis model, Ligustrazine decreased the expression of CD34 and VEGF in primary tumor tissue and reduced the number of metastasis nodi on the lung surface. Our data suggests that Ligustrazine may inhibit tumor metastasis, at least in part, through its anti-angiogenic activity.
AbstractList	Angiogenesis is crucial for tumor metastasis, with many compounds that inhibit tumor metastasis acting through suppression of angiogenesis. We investigated anti-angiogenic properties of Ligustrazine in a series of in vitro and in vivo models. Ligustrazine inhibited VEGF-induced HUVECs migration and tube formation in a dose-dependent manner in vitro, and had limited cytotoxicity to HUVECs and normal fibroblasts even at a dose up to 100 μg/ml. Ligustrazine also suppressed VEGF-induced rat aortic ring sprouting dose-dependently. In vivo, Ligustrazine reduced the Hb content in a Matrigel plug implanted in mice and inhibited new vessel formation in CAM. In addition, in a B16F10 spontaneous metastasis model, Ligustrazine decreased the expression of CD34 and VEGF in primary tumor tissue and reduced the number of metastasis nodi on the lung surface. Our data suggests that Ligustrazine may inhibit tumor metastasis, at least in part, through its anti-angiogenic activity. Angiogenesis is crucial for tumor metastasis, with many compounds that inhibit tumor metastasis acting through suppression of angiogenesis. We investigated anti-angiogenic properties of Ligustrazine in a series of in vitro and in vivo models. Ligustrazine inhibited VEGF-induced HUVECs migration and tube formation in a dose-dependent manner in vitro, and had limited cytotoxicity to HUVECs and normal fibroblasts even at a dose up to 100 microg/ml. Ligustrazine also suppressed VEGF-induced rat aortic ring sprouting dose-dependently. Invivo, Ligustrazine reduced the Hb content in a Matrigel plug implanted in mice and inhibited new vessel formation in CAM. In addition, in a B16F10 spontaneous metastasis model, Ligustrazine decreased the expression of CD34 and VEGF in primary tumor tissue and reduced the number of metastasis nodi on the lung surface. Our data suggests that Ligustrazine may inhibit tumor metastasis, at least in part, through its anti-angiogenic activity.Angiogenesis is crucial for tumor metastasis, with many compounds that inhibit tumor metastasis acting through suppression of angiogenesis. We investigated anti-angiogenic properties of Ligustrazine in a series of in vitro and in vivo models. Ligustrazine inhibited VEGF-induced HUVECs migration and tube formation in a dose-dependent manner in vitro, and had limited cytotoxicity to HUVECs and normal fibroblasts even at a dose up to 100 microg/ml. Ligustrazine also suppressed VEGF-induced rat aortic ring sprouting dose-dependently. Invivo, Ligustrazine reduced the Hb content in a Matrigel plug implanted in mice and inhibited new vessel formation in CAM. In addition, in a B16F10 spontaneous metastasis model, Ligustrazine decreased the expression of CD34 and VEGF in primary tumor tissue and reduced the number of metastasis nodi on the lung surface. Our data suggests that Ligustrazine may inhibit tumor metastasis, at least in part, through its anti-angiogenic activity. Angiogenesis is crucial for tumor metastasis, with many compounds that inhibit tumor metastasis acting through suppression of angiogenesis. We investigated anti-angiogenic properties of Ligustrazine in a series of in vitro and in vivo models. Ligustrazine inhibited VEGF-induced HUVECs migration and tube formation in a dose-dependent manner in vitro, and had limited cytotoxicity to HUVECs and normal fibroblasts even at a dose up to 100 microg/ml. Ligustrazine also suppressed VEGF-induced rat aortic ring sprouting dose-dependently. Invivo, Ligustrazine reduced the Hb content in a Matrigel plug implanted in mice and inhibited new vessel formation in CAM. In addition, in a B16F10 spontaneous metastasis model, Ligustrazine decreased the expression of CD34 and VEGF in primary tumor tissue and reduced the number of metastasis nodi on the lung surface. Our data suggests that Ligustrazine may inhibit tumor metastasis, at least in part, through its anti-angiogenic activity.
Author	Xu, Bo Zhang, Chang-bin Gao, Ming Zheng, Shi-zhong Wang, Ai-yun Chen, Lei Zhang, Li-juan Wu, Jia-ming Lei, Na Zhang, Wei-wei Lu, Yin
Author_xml	– sequence: 1 givenname: Lei surname: Chen fullname: Chen, Lei organization: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China – sequence: 2 givenname: Yin surname: Lu fullname: Lu, Yin email: luyingreen@126.com organization: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China – sequence: 3 givenname: Jia-ming surname: Wu fullname: Wu, Jia-ming organization: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China – sequence: 4 givenname: Bo surname: Xu fullname: Xu, Bo organization: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China – sequence: 5 givenname: Li-juan surname: Zhang fullname: Zhang, Li-juan organization: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China – sequence: 6 givenname: Ming surname: Gao fullname: Gao, Ming organization: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China – sequence: 7 givenname: Shi-zhong surname: Zheng fullname: Zheng, Shi-zhong organization: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China – sequence: 8 givenname: Ai-yun surname: Wang fullname: Wang, Ai-yun organization: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China – sequence: 9 givenname: Chang-bin surname: Zhang fullname: Zhang, Chang-bin organization: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China – sequence: 10 givenname: Wei-wei surname: Zhang fullname: Zhang, Wei-wei organization: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China – sequence: 11 givenname: Na surname: Lei fullname: Lei, Na organization: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China
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Snippet	Angiogenesis is crucial for tumor metastasis, with many compounds that inhibit tumor metastasis acting through suppression of angiogenesis. We investigated...
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SubjectTerms	Angiogenesis Angiogenesis Inhibitors - pharmacology Angiogenesis Inhibitors - therapeutic use Animals Cell Movement - drug effects Cell Proliferation - drug effects Female Fibroblasts - drug effects Humans Ligustrazine Lung Neoplasms - prevention & control Lung Neoplasms - secondary Melanoma, Experimental - blood supply Melanoma, Experimental - drug therapy Melanoma, Experimental - pathology Mice Mice, Inbred C57BL Microvessels - drug effects Neovascularization, Pathologic - chemically induced Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - pathology Pyrazines - pharmacology Pyrazines - therapeutic use Rats Tumor metastasis Vascular Endothelial Growth Factor A - pharmacology VEGF
Title	Ligustrazine inhibits B16F10 melanoma metastasis and suppresses angiogenesis induced by Vascular Endothelial Growth Factor
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