Anti-apoptotický mechanizmus metforminu proti apoptóze indukované ionizujícím zářením v mononukleárních buňkách lidské periferní krve
Authors:
S. Kolivand 1; E. Motevaseli 2,3; M. Cheki 4; A. Mahmoudzadeh 5; A. Shirazi 6; V. Fait 7
Authors‘ workplace:
Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences and Health Services
Tehran, Iran
1; Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences and Health Services
Tehran, Iran
2; Food Microbio logy Research Center, Tehran University of Medical Sciences and Health Services, Tehran, Iran
3; Department of Radiologic Technology, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
4; Department of Biosciences and Biotechnology, Malek Ashtar University of Technology, Tehran, Iran
5; Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences and Health Services, Tehran, Iran
6; Department of Surgical Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
7
Published in:
Klin Onkol 2017; 30(5): 372-379
Category:
Original Articles
doi:
https://doi.org/10.14735/amko2017372
Overview
Východiska:
V předchozím článku jsme ukázali, že metformin (MET) může snížit apoptózu indukovanou ionizační radiací (ionizing radiation – IR) v mononukleárních buňkách lidské periferní krve. Anti-apoptotický mechanizmus MET vůči IR však zůstává nejasný. Tato studie se pokouší ověřit mechanizmus působení MET v omezování rentgenem indukovanou apoptózu v mononukleárních buňkách lidské periferní krve.
Materiál a metody:
Mononukleární buňky byly 2 hod ošetřovány MET a ozářovány 6 Gy rentgenovými paprsky. Úrovně genové exprese BAX, CASP3 a BCL2 byly stanoveny 24 hod po ozáření za použití kvantitativní polymerázové řetězové reakce (qualitative polymerase chain reaction – qPCR) v reálném čase. Kromě toho byly hladiny proteinů BAX, CASP3 a BCL2 analyzovány pomocí metody Western blott.
Výsledky:
Radiační expozice zvýšila expresi genů BAX a CASP3 a snížila expresi genu BCL2 u mononukleárních buněk. Naopak, zvýšení exprese genu BCL2 spolu se snížením exprese genu BAX a CASP3 bylo pozorováno u MET a ozářených mononukleárních buněk. Bylo zjištěno, že záření zvýšilo poměr BAX/BCL2, zatímco MET snížil tento poměr. Také léčba s MET bez ozáření nezměnila expresi genů BAX, CASP3 a BCL2. Na druhou stranu snížená hladina proteinu BCL2 a zvýšená hladina proteinů BAX a CASP3 v 2 Gy ozářených mononukleárních buňkách, zatímco ovlivnění pomocí MET výrazně zvrátila tuto tendenci.
Závěr:
Výsledek naznačuje, že MET může chránit mononukleární buňky před apoptózou indukovanou IR prostřednictvím indukce buněčné anti-apoptotické signalizace.
Klíčová slova:
ionizující záření – metformin – apoptóza – geny – proteiny – krevní buňky
Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy.
Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů.
Obdrženo:
2. 8. 2017
Přijato:
7. 9. 2017
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