The Novel Vitamin D Analog ZK 191784 Inhibits Prostate Cancer Cell Invasion by Modulating Matrix Metalloproteinases and the Adhesion Molecule ICAM-1.
Gabriella Nesi, Maria Martinesi, Cristina Treves, Antonella Simoni, Maria Stio. University of Florence, Italy
Background: Low serum levels of 1,25(OH)2D3 (1,25D), thought to be the best indicator of vitamin D deficiency, have been associated with increased risk and a more aggressive biologic behavior of PCa. In this study, we examined the effects of 1,25D and its novel, low-calcemic analog ZK 191784 (ZK) on secreted matrix metalloproteinases (MMPs), as well as on the intercellular adhesion molecule-1 (ICAM-1) protein levels in human PCa cell lines LNCaP and DU-145. In order to assess the mechanisms of action of vitamin D derivatives, the expression of the vitamin D receptor (VDR) was estimated.
Design: Cells were incubated with vehicle (control), 1,25D or ZK, under serum-free conditions for 48 h. MMP-2 and MMP-9 activity was determined by gelatin zymography, while ICAM-1 and VDR levels were assessed by Western blot analysis and immunocytochemistry.
Results: 1,25D and ZK caused a marked decrease in the gelatinolytic activity of both MMP-2 and MMP-9 in DU-145 and LNCaP cell lines. Densitometric analysis showed a marked dose-dependent decrease in MMP activity compared to control, with a maximum reduction of MMP-2 and MMP-9 when ZK was used. VDR expression in cells treated with vitamin D derivatives was up-regulated over control. Contrariwise, ICAM-1 was down-regulated in the cells incubated with 1,25D or ZK.
Conclusions: These results support the possibility that vitamin D-based therapies may be beneficial in the prevention and management of advanced PCa.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 135, Monday Afternoon