Degarelix activity on cell growth and cell migration of three human prostate cancer cell lines

The direct effects of Degarelix (10-11-10-5M), a third generation GnRH antagonist, on prolif-eration and cell migration of three human prostate cancer lines (LNCaP, androgen-sensitive; DU145 and PC3, androgen-independent) have been explored. Moreover, the capability of De-garelix of counteracting the mitogenic activity and the cell migration due to EGF has been evaluated in DU145 cells. Cell counts were performed with a hemocytometer and the “scratch test assay” was used to evaluate cell migration. Statistical significance of the data was assessed by Student’s t test. In both LNCaP and PC3 cells, the antagonist reduced the growth (~15%, p<0.05) starting from the concentration of 2x10-8M. The inhibitory effect gradually increased reaching the maximum at the highest concentration used (10-5M, > 60%, p<0.0001). In LNCaP cells cul-tured in the presence of steroid-depleted serum, only 10-6 and 10-5M Degarelix reduced cell proliferation. In DU145 cells, Degarelix inhibited DU145 cell growth (~25%, p<0.01) starting from the concentration of 10-10M. This effect was seen up to the concentration of 10-7M, in-creased slightly at 10-6M (~35%, p<0.01) and was maximum at 10-5M (>60%, p<0.0001). EGF increased DU145 cell proliferation (~45%, p<0.01) and the addition of Degarelix reduced the stimulatory effect of the growth factor. Moreover, 50 ng/ml EGF increased (p<0.05), while 10-11M Degarelix inhibited (p<0.05) cell migration of DU145 cells. Finally, 10-11M Degarelix reduced (p<0.01) the cell migration induced by EGF. Our results clearly show that Degarelix has an inhibitory activity on proliferation of prostate cancer cell lines with different characteristics in terms of androgen sensitivity, differentiation and aggressiveness. This effect is observed at therapeutic concentrations of the GnRH antago-nist. In the androgen-independent DU145 cells, the lowest concentration of Degarelix(10-11M), which is ineffective on cell proliferation, reduces cell migration both in standard culture condition and in the presence of EGF. This phenomenon might be relevant in meta-static events.