Naslov (srp)

Uticaj semaglutida na progresiju mišjeg karcinoma dojke

Autor

Stanisavljević, Isidora, 1997-

Doprinosi

Pavlović, Slađana, 1976-
Jovanović, Ivan, 1977-
Mijatović, Sanja, 1967-
Petrović, Ivica, 1985-

Opis (srp)

Semaglutid, agonista receptora za glukagonu-sličan peptid 1, predstavljaantidijabetik koji pokazuje obećavajuća imunomodulatorna i antitumorska svojstva.Karcinom dojke predstavlja najčešći oblik maligniteta kod žena širom sveta. Ciljovog istraživanja bio je da se ispita uticaj semaglutida na rast i progresiju tumora,kao i na antitumorski imunski odgovor u 4T1 mišjem modelu karcinoma dojke. Nakonindukcije tumora, BALB/C miševi su intraperitonealno tretirani semaglutidom.Primena semaglutida odložila je pojavu palpabilnog tumora i usporila rastprimarnog tumora, kao i smanjila pojavu udaljenih metastaza u plućima i jetri. Leknije ispoljio direktno citotoksičko dejstvo na ćelijske linije mišjeg i humanogkarcinoma dojke in vitro, niti je značajno uticao na neoangiogenezu u tumorskom tkivu.Takođe, deplecija NK ćelija nije uticala na rast tumora kod miševa tretiranihsemaglutidom, što ukazuje na mehanizam nezavisan od NK ćelija. Aplikacijasemaglutida povećala je zastupljenost i sazrevanje CD11c⁺ dendritskih ćelija uslezini i tumorskom tkivu, istovremeno smanjujući zastupljenost CD4⁺CD25⁺FoxP3⁺regulatornih T limfocita i njihovu produkciju IL-10. Dodatno, semaglutid je povećaozastupljenost i citotoksičku aktivnost CD8⁺ T limfocita, što se ogleda u smanjenojekspresiji PD-1 i produkciji IL-10, a povećanju ekspresije CD69, NKG2D, CD107a igranzima B. Deplecijom CD8⁺ T limfocita neutralisan je antitumorski efekatsemaglutida, čime se potvrđuje da su ove ćelije ključna meta dejstva semaglutida.Rezultati ukazuju da semaglutid podstiče stečeni antitumorski imunski odgovor ipredstavlja potencijalno efikasan dodatni imunoterapijski agens u lečenjukarcinoma dojke.

Opis (srp)

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Opis (eng)

Semaglutide, a glucagon-like peptide-1 receptor agonist, is an antidiabetic that hasdemonstrated promising immunomodulatory and antitumor properties. Breast cancer is themost common form of malignancy among women worldwide. The aim of this study was toinvestigate the effects of semaglutide on tumor growth and progression, as well as on theantitumor immune response in the 4T1 murine model of breast cancer. Following tumorinduction, BALB/C mice were treated intraperitoneally with semaglutide. Semaglutideadministration delayed the onset of palpable tumors and slowed the growth of primarytumors, while reducing the occurrence of distant metastases in the lungs and liver. The drugdid not exhibit direct cytotoxic effects on murine or human breast cancer cell lines in vitro,nor did it significantly affect neovascularization in tumor tissue. Furthermore, NK celldepletion did not influence tumor growth in semaglutide-treated mice, indicating an NK cellindependent mechanism of action. Semaglutide treatment increased the presence andmaturation of CD11c⁺ dendritic cells in the spleen and tumor tissue, while simultaneouslyreducing the percentage of CD4⁺CD25⁺FoxP3⁺ regulatory T cells and their production of IL10. Additionally, semaglutide enhanced both the presence and cytotoxic activity of CD8⁺ Tcells, reflected in reduced expression of PD-1 and IL-10 production, alongside increasedexpression of CD69, NKG2D, CD107a, and granzyme B. Depletion of CD8⁺ T cellsneutralized the antitumor effect of semaglutide, confirming that CD8⁺ T cells are the keytarget of semaglutide’s action. These results suggest that semaglutide promotes an adaptiveantitumor immune response and represents a potentially effective adjunct immunotherapeuticagent in breast cancer treatment.

Jezik

srpski

Datum

2025

Licenca

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