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The disintegrin contortrostatin in combination with docetaxel is a potent inhibitor of prostate cancer in vitro and in vivo
Author(s) -
Lin Edwin,
Wang Qingcai,
Swenson Stephen,
Jadvar Hossein,
Groshen Susan,
Ye Wei,
Markland Francis S.,
Pinski Jacek
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21173
Subject(s) - docetaxel , prostate cancer , angiogenesis , in vivo , medicine , cancer research , matrigel , cd31 , prostate , cancer , cancer cell , biology , microbiology and biotechnology
BACKGROUND There are few available treatments for hormone refractory prostate cancer. Through the inhibition of integrins, contortrostatin (CN) effects tumor cell growth directly as well as through the inhibition of angiogenesis. The effect of CN in combination with docetaxel on prostate cancer cell lines in vitro and in vivo is evaluated in the present study. METHODS FACS analysis of integrin expression, assessment of CN and docetaxel exposure on viability of plated cancer cells, and scratch test migration analysis were performed on PC‐3 prostate cancer cells. CN and docetaxel inhibition of both PC‐3 and CWR‐22 prostate cancer cell lines were evaluated in a mouse xenograft bone model. Angiogenic activity in tumors were assessed using IHC with antibodies to CD31. RESULTS Cell culture experiments indicate that the combination of docetaxel and CN inhibits growth in an additive fashion. FACS analysis of PC‐3 cells shows expression of α5β1 and αvβ5 integrins, but little expression of the αvβ3. CN showed complete inhibition of PC‐3 migration in cultures grown on matrigel plates. In mice xenograft bone models, CN with docetaxel showed increased inhibition of both PC‐3 and CWR‐22 derived tumors. Analysis of treated xenograft tumors showed significantly decreased expression of CD31 indicating suppression of angiogenesis. Prostate 70:1359–1370, 2010. © 2010 Wiley‐Liss, Inc.