Abstract
This study investigated the use of low-dose metronomic (LDM) chemotherapy with paclitaxel in a highly metastatic mouse model of 4T1 breast cancers, and compared it with the maximum tolerable dose (MTD) therapy. LDM therapy displayed a stronger anti-tumor activity in suppressing primary and metastatic breast tumors with less degree of side effects, and stronger anti-angiogenic and anti-lymphangiogenic activities than MTD therapy. But MTD therapy showed stronger pro-apoptotic and anti-proliferative activities in situ. Paclitaxel therapy downregulated expression of vascular endothelial growth factor receptor-2 (VEGFR2) and up-regulated expression of thrombospondin-1. The results support the application of paclitaxel LDM therapy to treat advanced breast cancer.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / administration & dosage*
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Angiogenesis Inhibitors / toxicity
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Animals
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Antineoplastic Agents, Phytogenic / administration & dosage*
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Antineoplastic Agents, Phytogenic / toxicity
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Apoptosis / drug effects
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Breast Neoplasms / blood supply
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / metabolism
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Breast Neoplasms / secondary
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Endothelial Cells / drug effects
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Endothelial Cells / pathology
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Female
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Lymphangiogenesis / drug effects
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Maximum Tolerated Dose
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Mice
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Mice, Inbred BALB C
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / pathology
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Neovascularization, Pathologic / prevention & control*
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Paclitaxel / administration & dosage*
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Paclitaxel / toxicity
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Thrombospondin 1 / metabolism
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Time Factors
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Tumor Burden / drug effects
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents, Phytogenic
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Thrombospondin 1
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Vascular Endothelial Growth Factor Receptor-2
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Paclitaxel