Nitrogen-containing bisphosphonate, YM529/ONO-5920, inhibits tumor metastasis in mouse melanoma through suppression of the Rho/ROCK pathway.
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| Abstract |
The small GTPases of the Ras and Rho families are widely involved in tumorigenesis and metastasis. We recently showed that YM529/ONO-5920, a new developed bisphosphonate, inhibits the mevalonate pathway, is required for the prenylation of the small GTPases. In this study, we investigated whether YM529/ONO-5920 inhibits tumor cell migration, invasion, adhesion, and metastasis in B16BL6 cells, a mouse melanoma cell line. It was found that YM529/ONO-5920 significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not show anti-proliferative effects on B16BL6 cells. YM529/ONO-5920 also inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs). Furthermore, YM529/ONO-5920 suppressed Rho activation, but not activation of Ras. The results indicate that YM529/ONO-5920 suppresses the Rho/ROCK pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion and metastasis. These findings suggest that YM529/ONO-5920 has potential clinical applications for the treatment of tumour cell metastasis.
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| Authors | Yoshihiro Tanimori, Masanobu Tsubaki, Yuzuru Yamazoe, Takao Satou, Tatsuki Itoh, Yasuhiro Kidera, Masahi Yanae, Chikako Yamamoto, Junichi Kaneko, Shozo Nishida |
| Journal | Clinical & experimental metastasis (Clin Exp Metastasis) Vol. 27 Issue 7 Pg. 529-38 (Oct 2010) ISSN: 1573-7276 [Electronic] Netherlands |
| PMID | 20632074 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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