Abstract | BACKGROUND: METHODS:
CVS-3983 was administered i.p. twice-daily 7-days per week for 2-3 weeks to mice with established tumors. Measurements of tumor volume were made twice weekly. The effect of CVS-3983 on CWR22RV1 cell invasion through a reconstituted basement membrane matrix of proteins was also evaluated. Matriptase expression across the tumor lines was assessed by RT-PCR and Western blotting. RESULTS:
CVS-3983 inhibited final mean tumor volume by 65.5% (n = 10, P = 0.0002) in the CWR22R model and by 56.2% (n = 8, P = 0.0017) in the CWRSA6 tumor model compared with vehicle-treated tumors. CVS-3983 did not inhibit the proliferation of CWR22RV1 cells in vitro; however, the small molecule did significantly reduce by 30.2% the invasion of these cells in vitro through a reconstituted basement membrane matrix. Molecular analysis of the xenograft tumors demonstrated high expression levels of matriptase at the RNA and protein levels, which were not affected by CVS-3983 treatment. CONCLUSIONS: These results identify CVS-3983 as a potent inhibitor of AI prostate cancer cell invasion in vitro and established xenograft tumor growth in vivo.
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Authors | Anna V Galkin, Lynne Mullen, William D Fox, Jason Brown, David Duncan, Ofir Moreno, Edwin L Madison, David B Agus |
Journal | The Prostate
(Prostate)
Vol. 61
Issue 3
Pg. 228-35
(Nov 01 2004)
ISSN: 0270-4137 [Print] United States |
PMID | 15368474
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Copyright | 2004 Wiley-Liss, Inc. |
Chemical References |
- Androgens
- CVS-3983
- Membrane Proteins
- Oligopeptides
- Serine Proteinase Inhibitors
- Serine Endopeptidases
- matriptase
- St14 protein, mouse
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Topics |
- Androgens
(metabolism)
- Animals
- Extracellular Matrix
(enzymology)
- Female
- Male
- Membrane Proteins
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Oligopeptides
(chemistry, pharmacology)
- Prostatic Neoplasms
(drug therapy, metabolism, pathology)
- Serine Endopeptidases
(metabolism)
- Serine Proteinase Inhibitors
(chemistry, pharmacology)
- Tumor Cells, Cultured
- Xenograft Model Antitumor Assays
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