論文 - 詳細
| RRC ID | 67431 |
|---|---|
| 著者 | Tsubaki M, Satou T, Itoh T, Imano M, Ogaki M, Yanae M, Nishida S. |
| タイトル | Reduction of metastasis, cell invasion, and adhesion in mouse osteosarcoma by YM529/ONO-5920-induced blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathway. |
| ジャーナル | Toxicol Appl Pharmacol |
| Abstract |
Osteosarcoma is one of the most common primary malignant bone tumors in children and adolescents. Some patients continue to have a poor prognosis, because of the metastatic disease. YM529/ONO-5920 is a nitrogen-containing bisphosphonate that has been used for the treatment of osteoporosis. YM529/ONO-5920 has recently been reported to induce apoptosis in various tumors including osteosarcoma. However, the mode of metastasis suppression in osteosarcoma by YM529/ONO-5920 is unclear. In the present study, we investigated whether YM529/ONO-5920 inhibited tumor cell migration, invasion, adhesion, or metastasis in the LM8 mouse osteosarcoma cell line. We found that YM529/ONO-5920 significantly inhibited metastasis, cell migration, invasion, and adhesion at concentrations that did not have antiproliferative effects on LM8 cells. YM529/ONO-5920 also inhibited the mRNA expression and protein activities of matrix metalloproteinases (MMPs). In addition, YM529/ONO-5920 suppressed phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and the serine/threonine protein kinase B (Akt) by the inhibition of Ras prenylation. Moreover, U0126, a mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, and LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, also inhibited LM8 cell migration, invasion, adhesion, and metastasis, as well as the mRNA expression and protein activities of MMP-1, MMP-2, MMP-9, and MT1-MMP. The results indicated that YM529/ONO-5920 suppressed the Ras/MEK/ERK and Ras/PI3K/Akt pathways, thereby inhibiting LM8 cell migration, invasion, adhesion, and metastasis. These findings suggest that YM529/ONO-5920 has potential clinical applications for the treatment of tumor cell metastasis in osteosarcoma. |
| 巻・号 | 259(3) |
| ページ | 402-10 |
| 公開日 | 2012-3-15 |
| DOI | 10.1016/j.taap.2012.01.024 |
| PII | S0041-008X(12)00043-9 |
| PMID | 22326785 |
| MeSH | Animals Cell Adhesion / drug effects Cell Line, Tumor Cell Movement / drug effects Diphosphonates / pharmacology* Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors Gene Expression Regulation, Neoplastic / drug effects* Imidazoles / pharmacology* Male Matrix Metalloproteinases / genetics Matrix Metalloproteinases / metabolism Mice Mice, Inbred C3H Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors Neoplasm Invasiveness / prevention & control Neoplasm Metastasis / prevention & control* Osteosarcoma / drug therapy* Osteosarcoma / pathology Phosphoinositide-3 Kinase Inhibitors Proto-Oncogene Proteins c-akt / antagonists & inhibitors RNA, Messenger / metabolism ras Proteins / antagonists & inhibitors |
| IF | 3.347 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 50 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | LM8(RCB1450) |