Ketoprofen in Topical Formulation Decreases the Matrix Metalloproteinase-2 Expression and Pulmonary Metastatic Incidence in Nude Mice with Osteosarcoma
Ketoprofen in Topical Formulation Decreases the Matrix Metalloproteinase-2 Expression and Pulmonary Metastatic Incidence in Nude Mice with Osteosarcoma
复制标题
DOI：
10.1002/jor.20832
复制
发表时间：
2009-07-01
影响因子：
2.8
通讯作者：
Masuno, Hiroshi
中科院分区：
文献类型：
--
作者：
Kamei, Setsuya;Sakayama, Kenshi;Masuno, Hiroshi
本研究的目的是研究局部制剂中的酮洛芬（KP）是否影响皮下接种到雄性裸鼠背部空间的LM 8细胞的肿瘤生长和肺转移。接种后7天，用含KP的贴剂（KP组）或含安慰剂的贴剂（安慰剂组）局部治疗肿瘤3周。安慰剂组肺转移发生率为100%，KP组为60%。无肺转移的KP组（称为KP/转移（-）组）的肿瘤质量小于安慰剂组。进行增殖细胞核抗原（PCNA）、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）、基质金属蛋白酶-2（MMP-2）和血管内皮生长因子（VEGF）的免疫组织化学染色。与安慰剂组相比，KP/转移（-）组的肿瘤含有较少的PCNA阳性细胞和更多的TUNEL阳性细胞。在安慰剂组中，MMP-2和VEGF在肿瘤内广泛表达，而在KP/转移（-）组中，这两种蛋白的表达非常低。结论：KP局部治疗骨肉瘤可降低MMP-2和VEGF的表达，从而抑制肿瘤生长和肺转移。(C)2008骨科研究学会。出版社：Wiley Periodicals，Inc. J Orthop Res 27：909-915，2009
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. (C) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:909-915, 2009