Low-Dose Metronomic Paclitaxel Chemotherapy Suppresses Breast Tumors and Metastases in Mice

Hongchi JiangThe Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China, Department of Molecular Medicine & Pathology, Faculty of Medicine and Health Sciences, The University of Auckland, Auckland, New Zealand, Institute for Technology Research and Innovation, Institute of Biotechnology, Deakin University, Victoria, Australia

Weiyang TaoThe Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China, Department of Molecular Medicine & Pathology, Faculty of Medicine and Health Sciences, The University of Auckland, Auckland, New Zealand, Institute for Technology Research and Innovation, Institute of Biotechnology, Deakin University, Victoria, Australia

Mu ZhangThe Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China, Department of Molecular Medicine & Pathology, Faculty of Medicine and Health Sciences, The University of Auckland, Auckland, New Zealand, Institute for Technology Research and Innovation, Institute of Biotechnology, Deakin University, Victoria, Australia

Shangha PanThe Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China, Department of Molecular Medicine & Pathology, Faculty of Medicine and Health Sciences, The University of Auckland, Auckland, New Zealand, Institute for Technology Research and Innovation, Institute of Biotechnology, Deakin University, Victoria, Australia

Jagat R. KanwarThe Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China, Department of Molecular Medicine & Pathology, Faculty of Medicine and Health Sciences, The University of Auckland, Auckland, New Zealand, Institute for Technology Research and Innovation, Institute of Biotechnology, Deakin University, Victoria, Australia

Xueying SunThe Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China, Department of Molecular Medicine & Pathology, Faculty of Medicine and Health Sciences, The University of Auckland, Auckland, New Zealand, Institute for Technology Research and Innovation, Institute of Biotechnology, Deakin University, Victoria, AustraliaCorrespondence[email protected] [email protected]

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.

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ACKNOWLEDGMENTS

The work was supported by the Ministry of Science and Technology, China (2007BAI07A05), the Science and Technology Bureau of Heilongjiang Province, China (WH05C02), the National Natural Scientific Foundation of China (30571808,30872987), and the Creative Foundation for Postgraduates in Heilongjiang Province, China (YJSCX2008-112HLJ to W Tao).

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Low-Dose Metronomic Paclitaxel Chemotherapy Suppresses Breast Tumors and Metastases in Mice

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Low-Dose Metronomic Paclitaxel Chemotherapy Suppresses Breast Tumors and Metastases in Mice

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