Antitumorsko djelovanje niklozamida na stanice tumora mokraćnog mjehura

master's thesis

• Title (english): The antitumor effect of niclosamide on bladder cancer cells
• Author: Tina Domjanović
• Mentor: Jelena Korać Prlić (mentor)
• Mentor: Inga Urlić (komentor)
• Committee member: Inga Urlić (predsjednik povjerenstva)
• Committee member: Nada Oršolić (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Sofia Ana Blažević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-02-07, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Tumor mokraćnog mjehura deseti je najčešće dijagnosticirani oblik tumora u svijetu s jako
visokom stopom recidiva i niskom stopom preživljenja. Tradicionalne terapije najčešće imaju
teške nuspojave, a pacijenti gotovo uvijek razviju otpornost na liječenje. Niklozamid je
antiparazitski lijek koji se koristi za liječenje bolesti uzrokovanih trakavicama. Kod nekoliko
tipova tumora pokazano je njegovo antitumorsko djelovanje induciranjem apoptoze i
inhibicijom nekoliko signalnih puteva, kao što su WNT/CTNNB1, mTORC1, STAT3, NFκB,
Notch i Hedgehog. Budući da su njegove nuspojave i utjecaj na organizam već dijelom
istraženi, preusmjeravanje niklozamida prema liječenju tumora bilo bi kraće i jednostavnije od
razvoja novog lijeka. Cilj mog diplomskog rada bio je ispitati mehanizme antitumorskog
djelovanja niklozamida na stanice tumora mokraćnog mjehura; inducira li apoptozu i kakve
učinke ima na staničnu proliferaciju. Metodom western blot analizirala sam ekspresiju proteina,
a protočnom citometrijom apoptozu i stanični ciklus. Rezultati pokazuju da niklozamid inducira
apoptozu i zaustavlja proliferaciju stanica tumora mokraćnog mjehura. Stoga, niklozamid u
kombinaciji s postojećim lijekovima može imati potencijal za liječenje tumora mokraćnog
mjehura.

Abstract (english)

Bladder cancer is the 10th most common cancer worldwide, with a very high recurrence rate
and low survival rate. Traditional therapies often cause unpleasant side effects, and patients
develop drug resistance. Niclosamide is an antiparasitic medication that has been used for many
years to treat tapeworm infestations. In several types of tumors, niclosamide has been reported
to exhibit antitumor effects by inducing apoptosis and inhibiting several signaling pathways,
such as WNT/CTNNB1, mTORC1, STAT3, NFκB, Notch, and Hedgehog. As its adverse
effects have been partially investigated, repurposing niclosamide as a treatment for cancer
would be less time-consuming and less complicated than the development of a new drug. The
aim of my master thesis was to examine the mechanisms of the antitumor activity of
niclosamide on bladder cancer cells; does it induce apoptosis and what effects does it have on
cell proliferation. Protein expression was analyzed by western blotting, apoptosis analysis, and
cell cycle analysis using flow cytometry. These results demonstrate that niclosamide induces
apoptosis and inhibits the proliferation of bladder cancer cells. Therefore, niclosamide in
combination with existing drugs may have the potential to treat bladder tumors.

• Keywords: apoptoza; stanični ciklus; anithelmintik
• Keywords (english): apoptosis; cell cycle; anithelmintic
• Language: croatian
• URN:NBN: urn:nbn:hr:217:198625
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-03-08 11:31:04