DNA repair inhibitors as radiosensitizers in human lung cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F18%3A43889304" target="_blank" >RIV/60162694:G44__/18:43889304 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/18:10369717

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S1214021X16303416" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1214021X16303416</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jab.2017.10.008" target="_blank" >10.1016/j.jab.2017.10.008</a>

Jazyk výsledku

angličtina

Název v původním jazyce

DNA repair inhibitors as radiosensitizers in human lung cells

Popis výsledku v původním jazyce

The aim of this study was to compare the effects of DNA repair inhibitors in the context of radio-sensitization of human lung cells. The radio-sensitizing effects of NU7441 (1 mM), an inhibitor of DNA-dependent protein kinase (DNA-PK); KU55933 (10 μM), an inhibitor of ataxia-telangiectasia mutated kinase (ATM); and VE-821 (10 μM), an inhibitor of ATM-related kinase (ATR) were tested by the xCELLigence system for monitoring proliferation, fluorescence microscopy for DNA damage detection, flow-cytometry for cell cycle and apoptosis analysis and western blotting and ELISA for determination of DNA repair proteins. We employed normal human lung fibroblasts (NHLF, p53-wild-type) and non-small cell lung cancer cells (H1299, p53-negative). DNA-PK inhibition (by NU7441) in combination with ionizing radiation (IR) increased the number of double strand breaks (DSB), which persisted 72 h after irradiation in both cell lines. Additionally, NU7441 and KU55933 in combination with IR caused G2-arrest. ATR inhibitor (VE-821) together with IR markedly inhibited proliferation and induced G2/M arrest accompanied by apoptosis in H1299, but not in NHLF cells, and thus diminished DNA-repair of tumour cells but not normal lung fibroblasts. Our findings indicate that ATR inhibition could be a promising therapeutic strategy in p53-deficient lung tumours

Název v anglickém jazyce

DNA repair inhibitors as radiosensitizers in human lung cells

Popis výsledku anglicky

The aim of this study was to compare the effects of DNA repair inhibitors in the context of radio-sensitization of human lung cells. The radio-sensitizing effects of NU7441 (1 mM), an inhibitor of DNA-dependent protein kinase (DNA-PK); KU55933 (10 μM), an inhibitor of ataxia-telangiectasia mutated kinase (ATM); and VE-821 (10 μM), an inhibitor of ATM-related kinase (ATR) were tested by the xCELLigence system for monitoring proliferation, fluorescence microscopy for DNA damage detection, flow-cytometry for cell cycle and apoptosis analysis and western blotting and ELISA for determination of DNA repair proteins. We employed normal human lung fibroblasts (NHLF, p53-wild-type) and non-small cell lung cancer cells (H1299, p53-negative). DNA-PK inhibition (by NU7441) in combination with ionizing radiation (IR) increased the number of double strand breaks (DSB), which persisted 72 h after irradiation in both cell lines. Additionally, NU7441 and KU55933 in combination with IR caused G2-arrest. ATR inhibitor (VE-821) together with IR markedly inhibited proliferation and induced G2/M arrest accompanied by apoptosis in H1299, but not in NHLF cells, and thus diminished DNA-repair of tumour cells but not normal lung fibroblasts. Our findings indicate that ATR inhibition could be a promising therapeutic strategy in p53-deficient lung tumours

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Applied Biomedicine

ISSN

1214-021X

e-ISSN

—

Svazek periodika

16

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

9

Strana od-do

66-74

Kód UT WoS článku

000423027000011

EID výsledku v databázi Scopus

2-s2.0-85034989096