Nitrogen-containing bisphosphonate, YM529/ONO-5920, inhibits tumor metastasis in mouse melanoma through suppression of the Rho/ROCK pathway.
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.
Tanimori
Yoshihiro
Y
Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan.
Tsubaki
Masanobu
M
Yamazoe
Yuzuru
Y
Satou
Takao
T
Itoh
Tatsuki
T
Kidera
Yasuhiro
Y
Yanae
Masahi
M
Yamamoto
Chikako
C
Kaneko
Junichi
J
Nishida
Shozo
S
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D007093:Imidazoles / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D016133:Polymerase Chain Reaction; D054460:rho-Associated Kinases / Q000378:metabolism*
D017931:DNA Primers; D004164:Diphosphonates; D007093:Imidazoles; C087958:YM 529; D054460:rho-Associated Kinases