The concept of molecular tumor targeting might provide new hope in the treatment 
of advanced prostate cancer. We evaluated metastasis blocking properties of the 
histone deacetylase (HDAC) inhibitor valproic acid (VPA) and the mammalian 
target of rapamycin (mTOR) inhibitor RAD001 on prostate cancer cell lines. 
RAD001 or VPA were applied to PC-3 or LNCaP cells, either separately or in 
combination. Adhesion to vascular endothelium or to immobilized collagen, 
fibronectin or laminin was quantified. Migration and invasion were explored by a 
modified Boyden chamber assay. Integrin α and β subtypes were analyzed by flow 
cytometry, western blotting and RT-PCR. Effects of drug treatment on integrin 
related signaling, Akt and p70S6kinase activation, histone H3 and H4 acetylation 
were also determined. Separate application of RAD001 or VPA distinctly reduced 
tumor cell adhesion, migration and invasion, accompanied by elevated Akt 
activation and p70S6kinase de-activation. Integrin subtype expression was 
altered significantly by both compounds (VPA > RAD001). When both drugs were 
used in concert additive effects were observed on the migratory and invasive 
behavior but not on tumor-endothelium and tumor-matrix interaction. Separate 
mTOR or HDAC inhibition slows processes related to tumor metastasis. The 
RAD001-VPA combination showed advantage over VPA monotreatment with particular 
respect to migration and invasion. Ongoing studies are required to assess the 
relevance of VPA monotherapy versus VPA-RAD001 combination on tumor cell 
motility.