TGF-1抑制剂增加H460肺癌细胞的放射敏感性
TGF-β1 inhibitors increasing the radiosensitivity of H460 lung cancer cells
- 辐射研究与辐射工艺学报 2016年34卷第1期 页码：10202
- 作者机构：
1.苏州大学医学部放射医学与防护学院/放射医学及交叉学科研究院 苏州 215123
2.School of Radiation Medicine and Protection, Medical College/Schoolfor Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou 215123, China
- 作者简介：
黄浅漪，女，1992年出生，目前是苏州大学第二附属医院放射治疗科在读研究生，从事放射医学研究；E-mail: qianyi.huang@qq.com
杨红英，博士，教授，E-mail: yanghongying@suda.edu.cn
- 基金信息：国家自然科学基金(31270898, 11335011)、江苏省教育厅省属高校自然科学研究重大项目(12KJA310005)、江苏高校优势学科建设工程资助项目(PAPD)和苏州大学大学生莙政学者基金（黄浅漪）资助
DOI：10.11889/j.1000-3436.2016.rrj.34.010202
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黄浅漪, 赵一凡, 蒋友芹, 等. TGF-1抑制剂增加H460肺癌细胞的放射敏感性[J]. 辐射研究与辐射工艺学报, 2016,34(1):10202.
Qianyi HUANG, Yifan ZHAO, Youqin JIANG, et al. TGF-β1 inhibitors increasing the radiosensitivity of H460 lung cancer cells[J]. Journal of Radiation Research and Radiation Processing, 2016,34(1):10202.
黄浅漪, 赵一凡, 蒋友芹, 等. TGF-1抑制剂增加H460肺癌细胞的放射敏感性[J]. 辐射研究与辐射工艺学报, 2016,34(1):10202. DOI： 10.11889/j.1000-3436.2016.rrj.34.010202.
Qianyi HUANG, Yifan ZHAO, Youqin JIANG, et al. TGF-β1 inhibitors increasing the radiosensitivity of H460 lung cancer cells[J]. Journal of Radiation Research and Radiation Processing, 2016,34(1):10202. DOI： 10.11889/j.1000-3436.2016.rrj.34.010202.
摘要
摘要,探索一种TGF-β1受体激酶的选择性抑制剂SB431542对H460非小细胞肺癌细胞的放射增敏作用及对其DNA损伤应答体系的干扰。采用克隆形成实验检测SB431542对H460细胞放射敏感性的影响；用移植瘤实验验证SB431542在体内对H460细胞的放射增敏作用；采用流式细胞术检测细胞周期分布和细胞凋亡；用免疫荧光检测53BP1 foci和磷酸化的DNA-PKcs foci。结果发现，SB431542可增加H460的放射敏感性。照射前用SB431542预处理H460细胞虽然快速启动了细胞的DNA损伤应答反应，但却抑制了DNA双链断裂的非同源末端链接修复，因此，导致细胞残留更多未修复的DNA双链断裂，从而产生更严重的细胞周期阻滞。研究还发现，这种增敏作用与细胞凋亡无关。体内移植瘤实验表明，与单独照射组相比，连续3次用SB431542联合5 Gy的X-射线处理明显在处理后第5~12 d之间降低了肿瘤的生长。这些结果显示，在照射前用SB431542抑制肿瘤细胞的TGF-b1通路，能降低其DNA损伤修复能力，改变细胞周期分布，降低细胞克隆形成能力，延缓肿瘤的生长，因此用SB431542抑制TGF-b1通路可作为一些类型肺癌病人放疗的有效辅助手段。
Abstract
ABSTRACT ,The purpose of this study was to investigate theradiosensitizing effect of SB431542, a selective inhibitorof TGF-β1 receptor, on H460 non-small-cell lung cancer cells and relative interferingeffect on DNA damage response (DDR). Clonogenic assay was used to measure theradiosensitizing effects of SB431542 on H460 cells; xenograft mouse model wasused to study the radiosensitization ,in vivo,; flow cytometry was used todetermine cell cycle distribution and apoptosis; immunofluorescence microscopywas used to assess 53BP1 foci and pospho-DNA-PKcs foci. The results showed thatSB431542 could increase the radiosensitivity of H460 cells. Pretreatment ofH460 cells with SB431542 prior to irradiation initiated fast DDR but inhibitedDNA repair ,via, non-homologous end joining pathway and thus resulting inmore unrepaired DNA double strand breaks, which caused more severe cell cycledelay. However, apoptosis did not contribute to the radiosensitization. Thedata from xenograft model showed that compared with irradiation alone, thecombination of SB431542 and 5 Gy of X-rays on three consecutive dayssignificantly delayed the tumor growth from 5~12 d post treatment. All theabove indicate that inhibition of TGF-β1 pathway using SB431542 prior toirradiation can attenuate DNA damage repair and disturb cell cycledistribution, leading to decreased clonogenic cell survival and tumor growthdelay, which can be an effective adjunct in radiotherapy for certain lung cancersubtypes.
关键词
H460细胞TGF-β1抑制剂SB431542放射敏感性DNA损伤应答
Keywords
H460cellsTGF-β1Inhibitor SB431542RadiosensitivityDNA damage response
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