金纳米颗粒与低 LET 辐射的联合应用：增强 HT29 结直肠癌细胞系中 DNA DSB 诱导的一种方法。

Combination of gold nanoparticles with low-LET irradiation: an approach to enhance DNA DSB induction in HT29 colorectal cancer stem-like cells.

机构信息

Stem Cell Research Center, Golestan University of Medical Science, Gorgān, Iran.

Department of Biotechnology, College of Agriculture, Isfahan University of Technology, Isfahan, Iran.

出版信息

J Cancer Res Clin Oncol. 2019 Jan;145(1):97-107. doi: 10.1007/s00432-018-2769-3. Epub 2018 Oct 19.

DOI:10.1007/s00432-018-2769-3

PMID:30341685

Abstract

PURPOSE

High-linear energy transfer (high LET) irradiation has significant cytotoxic effects on different cancerous stem-like cells (CSLCs) such as colorectal CSLCs. A review of the literature has indicated that the presence of gold nanoparticles (GNPs) enables low-LET irradiation to produce highly non-homogeneous dose distributions like high-LET irradiation. The purpose of this study was to evaluate the radioresponsiveness of HT29 colorectal CSLCs under low-LET irradiation (X-ray) and in the presence of GNPs.

METHODS

Radioresponsiveness was evaluated using the ϒ-H2AX foci formation assay, the clonogenic assay, the cell cycle progression assay and analyses of radiobiological parameters.

RESULTS

In the presence of GNPs, the survival fraction of HT29 CSLCs was significantly reduced and caused significant changes in the radiobiological parameters after irradiation. In addition, ϒ-H2AX assay showed that in the presence of GNPs, the persistent DNA double-strand breaks were significantly increased in irradiated HT29 CSLCs. The relative biological effectiveness value of GNPs with X-rays was about 1.6 for HT-29 CSLCs at the 10% of cell survival fraction (D level) when compared to X-rays alone.

CONCLUSION

Therefore, the combination of GNPs with X-ray irradiation has the potential to kill HT29 CSLCs greater than the X-ray alone, and may be considered as an alternative for high-LET irradiation.

摘要

目的

高线性能量转移（high LET）辐射对不同的癌干细胞样细胞（CSLCs）具有显著的细胞毒性作用，例如结直肠 CSLCs。文献综述表明，金纳米粒子（GNPs）的存在使低 LET 辐射能够产生类似于高 LET 辐射的高度非均匀剂量分布。本研究旨在评估低 LET 辐射（X 射线）和存在 GNPs 时 HT29 结直肠 CSLC 的放射反应性。

方法

使用γ-H2AX 焦点形成测定、集落形成测定、细胞周期进展分析和放射生物学参数分析来评估放射反应性。

结果

在 GNPs 的存在下，HT29 CSLCs 的存活分数显著降低，并在照射后导致放射生物学参数发生显著变化。此外，γ-H2AX 测定表明，在 GNPs 的存在下，照射后的 HT29 CSLCs 中持续的 DNA 双链断裂明显增加。与单独使用 X 射线相比，当细胞存活分数（D 水平）为 10%时，用于 HT-29 CSLCs 的 GNPs 与 X 射线的相对生物效应值约为 1.6。