Terapeutski potencijal resveratrola i cisplatine na rast tumora miša u hipertermalnim uvjetima

master's thesis

• Title (english): Therapeutic potential of resveratrol and cisplatin on mouse tumor growth in hyperthermal conditions
• Author: Maria Prusina
• Mentor: Nada Oršolić (mentor)
• Mentor: Dyana Odeh (komentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Jasna Lajtner (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Petra Peharec Štefanić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2022-09-23, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Cilj ovog istraživanja bio je istražiti terapeutski potencijal resveratrola u kombinaciji s cisplatinom
na rast tumora u hipertermalnim uvjetima u miša, odnosno djelovanje ove kombinacije na inhibiciju
angiogeneze i rasta tumora te na polarizaciju makrofaga. Uz to, istraženo je može li višemodalni
pristup s hipertermijom i resveratrolom dokinuti otpornost tumorskih stanica na cisplatinu kroz
modulaciju aktivnosti histonskih deacetilaza (HDAC) i proteina toplinskog stresa te tako
doprinijeti izravnoj toksičnosti na tumorske stanice. Tumor je izazvan injiciranjem 1×106
stanica
EAT subkutano (sc) u bedro miševima soja Swiss albino. Miševi su obrađeni davanjem resveratrola
per os (po) u dozi od 50 mg/kg tijekom pet dana u nizu s početkom 2. dana od injiciranja tumora
i/ili cisplatinom koja je injicirana intaperitonealno (ip) u dozama od 2,5 mg/kg 10. i 12. dan te 5
mg/kg 15. dan. Neposredno nakon obrade miševi su izloženi sustavnoj hipertermiji tijekom 15
minuta pri temperaturi od 41 °C. Rezultati pokazuju da primjena resveratrola i cisplatine s
hipertermijom jest učinkovit pristup u terapiji tumora. Uspješno inhibira angiogenezu i rast tumora
te modulira polarizaciju makrofaga prema fenotipu M1. Također, dokida otpornost tumorskih
stanica na cisplatinu kroz modulaciju aktivnosti HDAC-a i razine šaperona HSP-70 i HSP-90 te
tako doprinosi povećanju životnog vijeka miševa.

Abstract (english)

The aim of this study was to investigate the therapeutic potential of resveratrol in combination with
cisplatin on mouse tumor growth in hyperthermal conditions, i.e. the effect of this combination on
inhibition of angiogenesis and tumor development, and on macrophage polarization. In addition, it
was investigated whether a multimodal approach with hyperthermia and resveratrol could abolish
cisplatin resistance in tumor cells through modulation of histone deacetylases (HDAC) activity and
heat shock proteins, contributing to direct toxicity on tumor cells. The tumor was induced by
injecting 1×106 EAT cells subcutaneously (sc) into the thighs of Swiss albino mice. Mice were
treated with resveratrol per os for five consecutive days beginning on day 2 after tumor injection
and/or by injecting cisplatin intraperitoneally (ip) at a dose of 2.5 mg/kg on days 10 and 12 and a
dose of 5 mg/kg on day 15. Immediately thereafter, mice were exposed to systematic hyperthermia
for 15 min at a temperature of 41 °C. Results show that the administration of resveratrol and
cisplatin with hyperthermia is an effective approach in tumor therapy. It successfully inhibits
angiogenesis and tumor growth and modulates macrophage polarization to the M1 phenotype.
Also, it abolishes tumor cells' cisplatin resistance through modulation of HDAC activity and
concentration of HSP-70 and HSP-90 chaperones, contributing to the increased lifespan of mice.

• Keywords: EAT; resveratrol; hipertermija; cisplatina; protutumorski učinak
• Keywords (english): EAT; resveratrol; hyperthermia; cisplatin; antitumor effect
• Language: croatian
• URN:NBN: urn:nbn:hr:217:927764
• 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; Embargo expiration date: 2024-09-23
• Created on: 2023-02-22 12:18:00