[Radiosensitizing effect of erlotinib on human lung adenocarcinoma cell line A549].
OBJECTIVE
To explore the radiosensitizing effect of erlotinib on human lung adenocarcinoma cell line A549 cells and the related mechanisms.


METHODS
The inhibitory effect of erlotinib on A549 cells was assessed by MTT assay, and its IC50 concentration was calculated. The radiosensitization was evaluated by the method of clone forming assay. Flow cytometry was used to analyze the effect of erlotinib on cell cycle and apoptosis.


RESULTS
The growth of A549 cells was inhibited after the cells were exposed to erlotinib for 48 hours. Moreover, the inhibitory rates increased with the increase of erlotinib concentrations, and IC50 was 19.26 µmol/L. In contrast to the irradiation alone group, the survival rates of the cells in erlotinib plus irradiation groups decreased, and erlotinib enhanced the radiosensitivity of the A549 cells. This effect was further increased as cells were exposed to erlotinib for a longer time. In the irradiation alone group and the two groups exposed to erlotinib for 24 hours and 48 hours before irradiation, D0 values were 3.01 Gy, 2.58 Gy and 2.45 Gy respectively, and Dq values were 2.16 Gy, 1.94 Gy and 1.61 Gy, respectively. In the last two groups, SERD0 values were 1.17 and 1.23, respectively. The flow cytometry analysis showed that erlotinib induced G2/M phase arrest and increased the apoptosis rate in A549 cells. With the increase of exposure time, the effects were more significant.


CONCLUSIONS
Erlotinib inhibits the A549 cell growth and enhances the radiosensitivity of A549 cells in vitro. The radiosensitizing mechanisms might be related to inhibiting repair of sublethal injury and inducing G2/M phase arrest and apoptosis.
Department of Oncology, Affiliated Jinshan Hospital, Fudan University, Shanghai 201508, China.
Xiao-qun
XQ
Liu
Department of Oncology, Affiliated Jinshan Hospital, Fudan University, Shanghai 201508, China. Email: tkqiao@yahoo.com.cn.
Tian-kui
TK
Qiao
D000230:Adenocarcinoma / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D010315:Particle Accelerators; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*
D011799:Quinazolines; D011838:Radiation-Sensitizing Agents; D000069347:Erlotinib Hydrochloride