碳离子放疗与常规光子放疗对表皮生长因子受体信号和神经胶质瘤细胞迁移影响的比较。

Impact of carbon ion irradiation on epidermal growth factor receptor signaling and glioma cell migration in comparison to conventional photon irradiation.

机构信息

Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, Mainz, Germany.

出版信息

Int J Radiat Biol. 2013 Jun;89(6):454-61. doi: 10.3109/09553002.2013.766769. Epub 2013 Feb 21.

DOI:10.3109/09553002.2013.766769

PMID:23363301

Abstract

PURPOSE

Radiotherapy of malignant gliomas may be limited by an interference of radiation with the migratory potential of tumor cells. Therefore, the influence of conventional photon and modern carbon ion ((12)C) irradiation on glioblastoma cell migration and on epidermal growth factor receptor-related (EGFR) signaling was investigated in vitro.

MATERIALS AND METHODS

EGFR overexpressing glioblastoma cell lines U87 EGFR++ and LN229 EGFR++ were irradiated with 0, 2 or 6 Gy photons or (12)C heavy ions. Migration was analyzed 24 h after treatment in a standardized Boyden Chamber assay. At different time points EGFR, protein kinase B (PKB/AKT) and extracellular signal-related kinases (ERK1/2) were analyzed by Western blotting.

RESULTS

2 Gy photon irradiation increased U87 EGFR++ migration and decreased motility of LN229 EGFR++ cells. Heavy ions decreased migration of both cell lines as a function of dose. There was a time-dependent increase of phosphorylation of EGFR, AKT and ERK1/2 in U87 EGFR++ after 2 Gy photon irradiation. After heavy ion irradiation EGFR, AKT or ERK1/2 remained unchanged.

CONCLUSIONS

Results suggest that the impact of irradiation on tumor cell migration depends on radiation type and cell line. Photons, but not heavy ions, potentially contribute to treatment failure by increasing EGFR-related tumor cell migration.

摘要

目的

恶性脑胶质瘤的放射治疗可能会受到肿瘤细胞迁移能力与放射干扰的限制。因此，本研究旨在体外探讨常规光子和现代碳离子（12C）照射对脑胶质瘤细胞迁移和表皮生长因子受体相关（EGFR）信号的影响。

材料与方法

用 EGFR 过表达的脑胶质瘤细胞系 U87 EGFR++和 LN229 EGFR++进行实验，分别用 0、2 或 6 Gy 的光子或 12C 重离子进行照射。在治疗后 24 小时，通过标准化的 Boyden 室测定分析细胞迁移。在不同时间点，通过 Western blot 分析 EGFR、蛋白激酶 B（PKB/AKT）和细胞外信号调节激酶（ERK1/2）。

结果

2 Gy 光子照射可增加 U87 EGFR++的迁移并降低 LN229 EGFR++细胞的迁移能力。重离子照射会降低两种细胞系的迁移能力，且这种作用与剂量呈正相关。U87 EGFR++在接受 2 Gy 光子照射后，EGFR、AKT 和 ERK1/2 的磷酸化水平呈时间依赖性增加。在重离子照射后，EGFR、AKT 或 ERK1/2 没有变化。