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.