Open AccessRadiosensitization of non-small cell lung carcinoma by EGFR inhibition
Author(s) -
D Otilija Keta,
Tanja Bulat,
Lela Korićanac,
Jelena Žakula,
G. Cuttone,
Giuseppe Privitera,
Ivan Petrović,
Aleksandra Ristíc-Fira
Publication year - 2014
Publication title -
nuclear technology and radiation protection
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.31
H-Index - 16
eISSN - 1452-8185
pISSN - 1451-3994
DOI - 10.2298/ntrp1403233k
Subject(s) - erlotinib , cancer research , epidermal growth factor receptor , radiosensitivity , lung cancer , adenocarcinoma , clonogenic assay , viability assay , medicine , cell growth , carcinoma , radiation therapy , dna repair , cell , pathology , biology , cancer , dna , genetics
Molecular targeted cancer therapy is a promising treatment strategy. Considering the central role of the epidermal growth factor receptor in cell proliferation and survival, there are indications that targeted agents like tyrosine kinase inhibitors, i. e., erlotinib, may enhance the antitumor treatment by radiation. The aim of this study is to analyze the inactivation effects of g-rays and to test the radiosensitizing potential of erlotinib on human lung adenocarcinoma cells in vitro. Irradiations were performed with doses ranging from 1 Gy to 8 Gy. In order to increase the radiosensitivity of CRL-5876 lung adenocarcinoma cells, the cells were treated with a clinically relevant concentration of 2 µM erlotinib. The effects of single and combined treatments were monitored using clonogenic survival, cell viability and proliferation assays at different time points. For the detection and visualization of the phosphorylated histone H2AX (γ-H2AX), an important biological marker of DNA double-strand break formation, fluorescence immunocytochemistry, was performed. The response to the treatment was monitored at four time points: 30 min, 2, 6, and 24 h. Irradiations with g-rays resulted in significant cell inactivation regarding all analyzed biological endpoints. Combined treatments revealed consistent cell inactivation. Moreover, compared to g-rays alone, elevated levels of g-H2AX foci were observed after pretreatment with erlotinib, indicating radiosensitization through impaired DNA repair. [Projekat Ministarstva nauke Republike Srbije, br. 173046 i br. 171019