Efekat metformina na vijabilitet i mitohondrijalni status tumorske i netumorske ćelijske linije

  • Jelena Ljubičič Medicinski fakultet Univerziteta u Beogradu
  • Andrej Pešić Univerzitetski Klinički Centar Srbije, Beograd, Srbija
  • Anđelka Isaković Institut za medicinsku i kliničku biohemiju, Medicinski fakultet Univerziteta u Beogradu
Ključne reči: metformin, karcinom pluća, mitohondrije

Sažetak


Sažetak

Uvod: Metformin predstavlja lek izbora u terapiji Diabetes mellitus-a tipa II, ali se u poslednjoj deceniji ističe njegov značajan antitumorski efekat u brojnim malignitetima. Mehanizam ovog efekta metformina je i dalje nedovoljno razjašnjen i predstavlja veliko polje istraživanja.

Cilj: Ispitivanje terapijskih koncentracija metformina na vijabilitet i mitohondrijalnu funkciju ćelija humanog nesitnoćelijskog karcinoma pluća (NCI-H460) kao i netumorskih imortalizovanih plućnih fibroblasta (MRC-5) u in vitro uslovima.

Materijal i metode: Vijabilitet ćelijskih linija NCI-H460 i MRC-5 nakon tretmana metforminom (10-60 µM) u trajanju od 1-7 dana određivan je testom aktivnosti kisele fosfataze i Crystal Violet metodom. Efekat metformina na parametre mitohondrijalne funkcije: depolarizaciju mitohondrija, produkciju superoksidnog anjona, reaktivnih kiseoničnih vrsta i na ukupnu masu mitohondrija ispitivan je pomoću protočnog citofluorimetra uz korišćenje JC-1, DHE, DHR i Mito Tracker fluorescentnih proba nakon 3, 24 i 120 h tretmana.

Rezultati: Metformin nije doveo do promene vijabiliteta kako tumorske, tako i netumorske ćelijske linije ni u jednoj terapijskoj koncentraciji i nezavisno od dužine trajanja tretmana. Povećanje depolarizacije mitohondrijalne membrane uočeno je nakon 3 h tretmana kod  netumorske MRC-5 ćelijske linije. Produžena ekspozicija metforminu (120 h) u tumorskoj NCI-H460 ćelijskoj liniji dovela je do povećanja produkcije superoksidnog anjona kao i ukupne mase mitohondrija. Promene u produkciji ukupnih reaktivnih kiseoničnih vrsta nisu primećene ni kod NCI-H460, ni kod MRC-5 ćelijske linije, tokom kratkotrajne ili produžene ekspozicije.

Zaključak: Meformin u terapijskim koncentracijama ne menja vijabilitet NCI-H460 i MRC-5 ćelija, ali indukuje akutnu depolarizaciju mitohondrijalne membrane u plućnim fibroblastima i povećanje produkcije superoksidnog anjona i mase mitohondrija u ćelijama plućnog karcinoma nakon produženog delovanja.

 

Biografija autora

Anđelka Isaković, Institut za medicinsku i kliničku biohemiju, Medicinski fakultet Univerziteta u Beogradu

Doc. dr 

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Objavljeno
2023/02/06
Broj časopisa
Vol. 73 Br. 4 (2022): Medicinski podmladak
Rubrika
Originalni naučni članak