RRC ID 19653
Author Kamei S, Sakayama K, Tamashiro S, Aizawa J, Miyawaki J, Miyazaki T, Yamamoto H, Norimatsu Y, Masuno H.
Title Ketoprofen in topical formulation decreases the matrix metalloproteinase-2 expression and pulmonary metastatic incidence in nude mice with osteosarcoma.
Journal J. Orthop. Res.
Abstract The aim of this study was to investigate whether ketoprofen (KP) in topical formulation affected the tumor growth and pulmonary metastasis of LM8 cells, which were inoculated subcutaneously into the back space of male nude mice. At 7 days after inoculation, the tumor was treated topically for 3 weeks with either a KP-containing patch (KP group) or a placebo-containing patch (placebo group). The pulmonary metastatic incidence was 100% in the placebo group and 60% in the KP group. The tumor mass of the KP group without pulmonary metastasis, termed the KP/metastasis(-) group, was smaller than that of the placebo group. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), matrix metalloproteinase-2 (MMP-2), and vascular endothelial growth factor (VEGF) was performed. The tumors of the KP/metastasis(-) group contained fewer PCNA-positive cells and many more TUNEL-positive cells in comparison to the placebo group. In the placebo group, MMP-2 and VEGF were extensively expressed within the tumor, whereas in the KP/metastasis(-) group the expression of these two proteins was very low. In conclusion, the topical treatment of osteosarcoma with KP decreased the expression of MMP-2 and VEGF, thus resulting in the suppression of tumor growth and pulmonary metastasis.
Volume 27(7)
Pages 909-15
Published 2009-7
DOI 10.1002/jor.20832
PMID 19105229
MeSH Administration, Topical Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology* Antigens, CD34 / metabolism Apoptosis / drug effects Cell Line, Tumor In Situ Nick-End Labeling Incidence Ketoprofen / pharmacology* Lung Neoplasms / drug therapy* Lung Neoplasms / mortality Lung Neoplasms / secondary Male Matrix Metalloproteinase 2 / metabolism* Mice Mice, Nude Neoplasm Transplantation Neovascularization, Pathologic / drug therapy Neovascularization, Pathologic / mortality Osteosarcoma / drug therapy* Osteosarcoma / mortality Osteosarcoma / secondary Survival Rate Vascular Endothelial Growth Factor A / metabolism
IF 3.414
Times Cited 9
Human and Animal Cells LM8 (RCB1450)