Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects of macrolide antibiotics on tumor angiogenesis, tumor growth and metastasis in the B 16BL6 mouse melanoma and C57BL mouse system. Two 14-membered ring macrolide antibiotics, roxithromycin and clarithromycin, significantly reduced the dense capillary network area in a mouse dorsal air sac angiogenesis model, whereas a 15-membered ring macrolide, azithromycin, and a 16-membered ring macrolide, josamycin, did not show any inhibitory effect on angiogenesis at the same dose. Intraperitoneal administration of roxithromycin and clarithromycin at 50 mg/kg/day reduced the tumor size of B 16BL6 melanoma to about 41% and 56%, respectively, of that of the control, and significantly suppressed pulmonary metastasis of B16BL6 cells in a spontaneous system. Azithromycin and josamycin, on the other hand, did not inhibit tumor growth or pulmonary metastasis of B16BL6 cells. Immunohistochemistry revealed that roxithromycin and clarithromycin reduced the tumor vascularity and increased apoptosis of the tumor cells in vivo. These results suggest that 14-membered ring macrolides have antiangiogenic and antitumor effects and might have possible therapeutic applications.
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PMID:Antiangiogenic and antitumor effects of 14-membered ring macrolides on mouse B16 melanoma cells. 1054 23

Tumor angiogenesis is essential during lung cancer development and targeting angiogenesis may possess a potential therapeutic value. The present study demonstrates that azithromycin, a Food and Drug Administration-approved antibiotic drug, is a novel tumor angiogenesis inhibitor. Azithromycin inhibits capillary network formation of human lung tumor associated-endothelial cells (HLT-ECs) in vitro and in vivo. It significantly inhibits HLT-EC adhesion and vascular endothelial growth factor (VEGF)-induced proliferation of HLT-ECs in a dose-dependent manner without affecting migration. In addition, azithromycin induces apoptosis of HLT-ECs even in the presence of VEGF. Notably, azithromycin inhibits proliferation and induces apoptosis in multiple lung cancer cell lines to a significantly reduced extent compared with in HLT-ECs, suggesting that HLT-ECs are more susceptible to azithromycin treatment. In a lung tumor xenograft model, azithromycin significantly inhibits tumor growth and its anti-tumor activities are achieved by suppressing angiogenesis. Notably, the inhibitory effects of azithromycin on angiogenesis are associated with its ability to suppress VEGF-induced activation of VEGF receptor 2 (VEGFR2), phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), focal adhesion kinase, and disruption of focal adhesion assembly and actin stress fiber formation in HLT-ECs. The present study identifies that azithromycin targets VEGFR2-mediated focal adhesion and PI3K/Akt signaling pathways in HLT-ECs, leading to the suppression of angiogenesis and lung tumor growth.
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PMID:Azithromycin effectively inhibits tumor angiogenesis by suppressing vascular endothelial growth factor receptor 2-mediated signaling pathways in lung cancer. 2869 39