Utjecaj statina na stanične linije karcinoma prostate čovjeka u 2D i 3D uvjetima rasta in vitro

master's thesis

• Title (english): Effect of statins on human prostate cancer cell lines in 2D and 3D growth conditions in vitro
• Author: Klara Uhrl
• Mentor: Maja Sabol (mentor)
• Mentor: Nada Oršolić (komentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Domagoj Đikić (član povjerenstva)
• Committee member: Inga Urlić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2025, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

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.

Abstract (english)

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 kallikrein related peptidase 2 (KLK2) in two dimensional and three dimensional cell cultures. Cells grown in three dimensional conditions show weaker or even opposite response to treatments indicating the resistance to these compounds.

• Keywords: karcinom prostate; kolesterol; androgeni receptor; statini
• Keywords (english): prostate cancer; cholesterol; androgen receptor; statins
• Language: croatian
• URN:NBN: urn:nbn:hr:217:059309
• Project: Number: IP-2022-10-6672; Title: Uloga signalnog puta Hedgehog-GLI u komunikaciji tumora i strome posredovanoj faktorima rasta u 2D i 3D tumorskim modelima; Title: The role of Hedgehog-GLI signaling in growth factor-mediated tumor-stroma communication in 2D and 3D in vitro tumor models; Acronym: HHgrow3D; Leader: Maja Sabol; Jurisdiction: Croatia; Funder: Hrvatska zaklada za znanost; Funding stream: Research Projects
• Study programme: Title: Experimental Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra eksperimentalne biologije (sveučilišni/a magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-01-27 13:19:11