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IJBB Vol.42(6) [December 2005] >

Title: Correlation of HER1/EGFR expression and degree of radiosensitizing effect of the HER1/EGFR-tyrosine kinase inhibitor erlotinib
Authors: Kim, Jae-Chul
Ali, M Aktar
Nandi, Animesh
Mukhopadhyay, Partha
Choy, Hak
Cao, Carolyn
Saha, Debabrata
Keywords: Epidermal growth factor (EGF)
HER1/EGFR inhibitor
HER1/EGFR expression
Lung cancer
Cell lines A431, H157 and H460
Flow cytometric analysis
Cell cycle analysis
Tyrosine kinase activity
Issue Date: Dec-2005
Publisher: CSIR
IPC CodeC12N 15/52
Abstract: Epidermal growth factor receptor (HER1/EGFR)-mediated signal transduction pathways are important in cellular response to ionizing radiation. High HER1/EGFR expression on cancer cells may contribute to radioresistance. In this pre-clinical study, we evaluated the radiosensitizing effect of erlotinib, a small molecule HER1/EGFR inhibitor in three human cancer cell lines with different HER1/EGFR expression — A431 (very high expression), H157 (moderate expression) and H460 (low expression). Our results demonstrated that A431 was the most radioresistant, while H460 was the most radiosensitive. However, A431 cells were the most sensitive to erlotinib (IC₅₀ = 300 nM) and H460 cells the most resistant (IC₅₀ = 8 μM). H157 had intermediate sensitivity to radiation and erlotinib (IC₅₀ = 3 μM). With 300 nM erlotinib, the radiation dose enhancement ratios (DER) were 1.40, 1.17 and 1.04 in A431, H157 and H460, respectively. Treatment with erlotinib for 24 hr at 300 nM increased G1 arrest by 18.6, 2.0 and 4.8% in A431, H157 and H460, respectively. Erlotinib-induced apoptosis was augmented by radiation in A431 cells only. In conclusion, high HER1/EGFR expression may result in a high degree of radiosensitization with erlotinib combined with radiation. The extent of erlotinib-induced radiosensitization was proportional to HER1/EGFR expression, as well as autophosphorylation of the human epidermal growth factor receptor (HER1/EGFR).
Page(s): 358-365
ISSN: 0301-1208
Source:IJBB Vol.42(6) [December 2005]

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