Low-dose metronomic paclitaxel chemotherapy suppresses breast tumors and metastases in mice.
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.
Jiang
Hongchi
H
The Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
Tao
Weiyang
W
Zhang
Mu
M
Pan
Shangha
S
Kanwar
Jagat R
JR
Sun
Xueying
X
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D042583:Lymphangiogenesis / Q000187:drug effects; D020714:Maximum Tolerated Dose; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000633:toxicity; D019700:Thrombospondin 1 / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D019700:Thrombospondin 1; D040301:Vascular Endothelial Growth Factor Receptor-2; D017239:Paclitaxel