Repozitorij Univerze v Novi Gorici

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Naslov:Vpliv metformina in sorodnih ksenobiotikov na viabilnost celic raka dojke
Avtorji:ID Petan, Toni (Mentor) Več o mentorju... Novo okno
ID Klemenčič, Sara (Avtor)
Datoteke:.pdf Sara_Klemencic.pdf (1,08 MB)
MD5: 21999C44C956F4941D3D89A89DF9F2D2
 
Jezik:Slovenski jezik
Vrsta gradiva:Diplomsko delo/naloga
Tipologija:2.11 - Diplomsko delo
Organizacija:FZO - Fakulteta za znanosti o okolju
Opis:Farmacevtska industrija se danes med drugim sooča tudi z negativnimi vplivi svojih proizvodov na okolje. Tak primer je metformin, ki spada med najpogosteje predpisana zdravila v procesih zdravljenja diabetesa tipa II in je hkrati v fazi kliničnih raziskav kot zdravilo za zdravljenje rakavih obolenj. Deluje tako, da zavira celično dihanje, niža proizvodnjo ATP in aktivira z AMP-aktivirano protein kinazo (AMPK), ki je glavni metabolični senzor v evkariontskih celicah. V diplomskem delu smo želeli ugotoviti, ali metformin in sorodni ksenobiotiki, povezani z delovanjem AMPK (spojina C in bromokrotonska kislina), vplivajo na rast visoko invazivnih celic adenokarcinoma dojke MDA-MB-231. To smo storili s pomočjo spektrofluorimetričnega testa viabilnosti z barvilom Presto Blue, ki temelji na sposobnosti zdravih celic, da reducirajo barvilo po vstopu v celico. Pokazali smo, da obstaja linearna zveza med številom celic MDA-MB-231 v populaciji in fluorescenčnim signalom barvila, kar potrjuje ustreznost izbrane metode. Celice smo gojili 48 h pri optimalnih pogojih in v prisotnosti različnih koncentracij vsake od treh učinkovin. Pokazali smo, da viabilnost celic pojema z naraščanjem koncentracije učinkovine. Rezultati kažejo, da inhibicija kataboličnih in oksidativnih procesov v celici (mitohondrijsko dihanje, oksidacija maščobnih kislin in aktivacija AMPK) negativno vpliva na rast in preživetje celic MDA-MB-231. Z našimi rezultati smo prispevali k boljšemu razumevanju mehanizma delovanja metformina in sorodnih zdravilnih učinkovin usmerjenih proti kataboličnemu metabolizmu.
Ključne besede:viabilnost, metformin, bromokrotonska kislina, spojina C, dorzomorfin, AMPK, rak dojke, MDA-MB-231
Kraj izida:Nova Gorica
Leto izida:2017
PID:20.500.12556/RUNG-2912-eb200a1e-4852-2a5c-0cc8-42e3bb3af166 Novo okno
COBISS.SI-ID:4650491 Novo okno
NUK URN:URN:SI:UNG:REP:IH2OH7AY
Datum objave v RUNG:31.01.2017
Število ogledov:15137
Število prenosov:253
Metapodatki:XML DC-XML DC-RDF
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Sekundarni jezik

Jezik:Ni določen
Naslov:The effect of metformin and associated xenobiotics on the viability of breast cancer cells
Opis:The pharmaceutical industry is often confronted with the negative effects of their products on the environment. A good example is metformin, one of the most frequently prescribed drugs in the treatment of type II diabetes, which is currently also in clinical trials for the treatment of cancer. It inhibits cell respiration, reduces the production of ATP and activates AMP-activated protein kinase (AMPK), which is the main metabolic sensor in eukaryotic cells. The aim of this work was to determine whether metformin and related xenobiotics, associated with the activity of AMPK (compound C and bromocrotonic acid), affect the growth of the highly invasive MDA-MB-231 breast adenocarcinoma cells. The effects of these pharmacological agents on breast cancer cell growth were determined with a spectrofluorimetric viability assay using the Presto Blue dye, which is based on its ability to undergo reduction upon entering healthy cells. We found that there is a linear relationship between the number of MDA-MB-231 cells in the population and Presto Blue fluorescence intensity, which confirms the suitability of the chosen method. The cells were cultured for 48 h under optimal conditions in the presence of various concentrations of each of the three compounds. The results show that the viability of MDA-MB-231 cells decreases with increasing concentrations of each agent. This suggests that inhibition of catabolic and oxidative processes in MDA-MB-231 cells (mitochondrial respiration, fatty acid oxidation and activation of AMPK) adversely affects their growth and survival. Our results contribute to a better understanding of the mechanism of action of metformin and other pharmacological agents targeting catabolic metabolism.
Ključne besede:cell viability, metformin, bromocrotonic acid, compound C, dorsomorphin, AMPK, breast cancer, MDA-MB-231


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