Effects of siRNA TMPRSS2-ERG combined with antiandrogens in prostate cancer

Cilj ovog rada je bio pronaći prikladnu terapiju za rak prostate kombinacijom dva različita pristupa, hormonalne i genske terapije. Monoterapija antiandrogenima se koristi pri liječenju raka prostate, a mehanizam se zasniva na blokiranju androgen receptora. Genska terapija se u ovom slučaju bazira na činjenici da se u više od 50 % slučajeva raka prostate nalazi fuzija TMPRSS2-ERG. Dakle, cilj je bio kombinirati flutamid (nesteroidni antiandrogen) sa siRNA TMPRSS2-ERG kako bi se smanjila ekspresija TMPRSS2-ERG mRNA i ERG proteina in vitro, te rast tumora in vivo. U eksperimentalnom dijelu rada korišteni su VCaP stanična linija te SCID miševi. Rezultati pokazuju da kombinacija flutamida i siRNA TMPRSS2-ERG nije poboljšala djelovanje flutamida na ekspresiju TMPRSS2-ERG in vitro, kao ni rast tumora in vivo.The aim of this thesis was to find appropriate treatment for prostate cancer by combination of two different approaches. The first one is based on the antiandrogen monotherapy which is used as conventional therapy of prostate cancer and the second one on the fact that prostate cancers carry oncofusion TMPRSS2-ERG in more than 50 % of cases. The idea was to combine flutamide (a nonsteroidal antiandrogen) with siRNA (designed against TMPRSS2-ERG fusion) in order to reduce TMPRSS2-ERG mRNA expression and ERG protein expression in vitro, and to reduce tumor growth in vivo. Studies are performed on VCaP cell line and SCID mice. Our results showed that the combination of flutamide and siRNA TMPRSS2-ERG did not enhance either in vitro, cell death and TMPRSS2-ERG inhibition or in vivo the tumor regression. This suggests that the siRNA TMPRSS2-ERG can be used as an alternative in androgen-independent phase