Utjecaj statina na stanične linije karcinoma prostate čovjeka u 2D i 3D uvjetima rasta in vitro ; Effect of statins on human prostate cancer cell lines in 2D and 3D growth conditions in vitro

Statini su inhibitori 3-hidroksi-3-metilglutaril koenzim A reduktaze (HMGCR) koji blokirajući aktivnost ovog enzima smanjuju razinu kolesterola u stanicama. S obzirom na svoj reducirajući učinak na kolesterol, statini se uglavnom koriste za liječenje kardiovaskularnih bolesti. Usprkos svojoj širokoj primjeni u liječenju bolesti krvožilnog sustava, brojna pretklinička istraživanja dokazala su antineoplastični učinak statina na neke vrste tumora poput kolorektalnog karcinoma ili karcinoma prostate (PCa). U ovom radu ispitivali smo učinak simvastatina i lovastatina na stanice karcinoma prostate (LNCaP i PC3) te fibroblasta prostate (WPMY-1) u dvodimenzionalnim i trodimenzionalnim uvjetima rasta. Tri stanične linije pokazuju različitu osjetljivost na statine, pri čemu su LNCaP stanice najotpornije u oba uvjeta rasta. Oba statina smanjuju ekspresiju AR (gen za androgeni receptor), PSA (antigen specifičan za prostatu) i KLK2 (kalikrein 2) gena u 2D i 3D staničnim kulturama. Stanice uzgojene u trodimenzionalnim uvjetima pokazuju slabiji ili čak suprotan odgovor na tretmane što ukazuje na rezistenciju na ove spojeve. ; Statins are inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) which, by blocking the activity of this enzyme, reduce the level of cholesterol in the cells. Due to their cholesterol-lowering effect, statins are mainly used to treat cardiovascular diseases. Despite their wide application in treatment of vascular diseases, numerous preclinical studies found antineoplastic effect of statins on different tumors such as colon or prostate cancer. In this work, we investigated the effect of simvastatin and lovastatin on the prostate cancer cells (LNCaP and PC3) and prostate fibroblasts (WPMY-1) in two dimensional and three dimensional growth conditions. The three cell lines show different sensitivity to statins, with LNCaP cells being the most resistant in both growth conditions. Both statins downregulate the expression of androgen receptor gene (AR), prostate specific antigen (PSA) and ...