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CVS-3983, a selective matriptase inhibitor, suppresses the growth of androgen independent prostate tumor xenografts.
Prostate 2004; 61(3):228-35P

Abstract

BACKGROUND

Matriptase, a type-II transmembrane serine protease, is expressed by cancers of epithelial origin including breast, colon, and prostate carcinomas and has been implicated in tumor growth and progression. We studied the effects of CVS-3983, a selective small molecule matriptase inhibitor, on the growth of the androgen independent (AI) CWR22R and CWRSA6 human prostate cancer xenograft models.

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.

Authors+Show Affiliations

Cedars-Sinai Louis Warschaw Prostate Cancer Center, Los Angeles, California 90045, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15368474

Citation

Galkin, Anna V., et al. "CVS-3983, a Selective Matriptase Inhibitor, Suppresses the Growth of Androgen Independent Prostate Tumor Xenografts." The Prostate, vol. 61, no. 3, 2004, pp. 228-35.
Galkin AV, Mullen L, Fox WD, et al. CVS-3983, a selective matriptase inhibitor, suppresses the growth of androgen independent prostate tumor xenografts. Prostate. 2004;61(3):228-35.
Galkin, A. V., Mullen, L., Fox, W. D., Brown, J., Duncan, D., Moreno, O., ... Agus, D. B. (2004). CVS-3983, a selective matriptase inhibitor, suppresses the growth of androgen independent prostate tumor xenografts. The Prostate, 61(3), pp. 228-35.
Galkin AV, et al. CVS-3983, a Selective Matriptase Inhibitor, Suppresses the Growth of Androgen Independent Prostate Tumor Xenografts. Prostate. 2004 Nov 1;61(3):228-35. PubMed PMID: 15368474.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CVS-3983, a selective matriptase inhibitor, suppresses the growth of androgen independent prostate tumor xenografts. AU - Galkin,Anna V, AU - Mullen,Lynne, AU - Fox,William D, AU - Brown,Jason, AU - Duncan,David, AU - Moreno,Ofir, AU - Madison,Edwin L, AU - Agus,David B, PY - 2004/9/16/pubmed PY - 2004/11/13/medline PY - 2004/9/16/entrez SP - 228 EP - 35 JF - The Prostate JO - Prostate VL - 61 IS - 3 N2 - BACKGROUND: Matriptase, a type-II transmembrane serine protease, is expressed by cancers of epithelial origin including breast, colon, and prostate carcinomas and has been implicated in tumor growth and progression. We studied the effects of CVS-3983, a selective small molecule matriptase inhibitor, on the growth of the androgen independent (AI) CWR22R and CWRSA6 human prostate cancer xenograft models. 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. SN - 0270-4137 UR - https://www.unboundmedicine.com/medline/citation/15368474/CVS_3983_a_selective_matriptase_inhibitor_suppresses_the_growth_of_androgen_independent_prostate_tumor_xenografts_ L2 - https://doi.org/10.1002/pros.20094 DB - PRIME DP - Unbound Medicine ER -