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[厄洛替尼对人肺腺癌细胞系A549的放射增敏作用]

[Radiosensitizing effect of erlotinib on human lung adenocarcinoma cell line A549].

作者信息

Liu Xiao-qun, Qiao Tian-kui

机构信息

Department of Oncology, Affiliated Jinshan Hospital, Fudan University, Shanghai 201508, China.

Department of Oncology, Affiliated Jinshan Hospital, Fudan University, Shanghai 201508, China. Email:

出版信息

Zhonghua Zhong Liu Za Zhi. 2013 Nov;35(11):819-23.

Abstract

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.

摘要

目的

探讨厄洛替尼对人肺腺癌细胞系A549细胞的放射增敏作用及其相关机制。

方法

采用MTT法评估厄洛替尼对A549细胞的抑制作用,并计算其IC50浓度。通过克隆形成试验方法评估放射增敏作用。采用流式细胞术分析厄洛替尼对细胞周期和凋亡的影响。

结果

A549细胞暴露于厄洛替尼48小时后生长受到抑制。此外,抑制率随厄洛替尼浓度增加而升高,IC50为19.26 μmol/L。与单纯照射组相比,厄洛替尼联合照射组细胞存活率降低,厄洛替尼增强了A549细胞的放射敏感性。随着细胞暴露于厄洛替尼时间延长,这种作用进一步增强。在单纯照射组以及照射前暴露于厄洛替尼24小时和48小时的两组中,D0值分别为3.01 Gy、2.58 Gy和2.45 Gy,Dq值分别为2.16 Gy、1.94 Gy和1.61 Gy。后两组的SERD0值分别为1.17和1.23。流式细胞术分析显示,厄洛替尼诱导A549细胞G2/M期阻滞并增加凋亡率。随着暴露时间增加,作用更显著。

结论

厄洛替尼在体外抑制A549细胞生长并增强A549细胞的放射敏感性。放射增敏机制可能与抑制亚致死损伤修复、诱导G2/M期阻滞和凋亡有关。

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