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125I粒子持续低剂量率辐射与60Co高剂量率γ辐射对非小细胞肺癌细胞生物学效应的比较

A comparison of the biological effects of 125I seeds continuous low-dose-rate radiation and 60Co high-dose-rate gamma radiation on non-small cell lung cancer cells.

作者信息

Wang Zhongmin, Zhao Zhenzhen, Lu Jian, Chen Zhijin, Mao Aiwu, Teng Gaojun, Liu Fenju

机构信息

Institution of Molecular Imaging, Southeast University, Nanjing, China; Department of Interventional Radiology, The Third Affiliated Hospital of the Medical College Shihezi University, Xinjiang, China; Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Radiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Interventional Radiology, Shanghai St. Luke's Hospital, Shanghai, China.

出版信息

PLoS One. 2015 Aug 12;10(8):e0133728. doi: 10.1371/journal.pone.0133728. eCollection 2015.

Abstract

OBJECTIVES

To compare the biological effects of 125I seeds continuous low-dose-rate (CLDR) radiation and 60Co γ-ray high-dose-rate (HDR) radiation on non-small cell lung cancer (NSCLC) cells.

MATERIALS AND METHODS

A549, H1299 and BEAS-2B cells were exposed to 125I seeds CLDR radiation or 60Co γ-ray HDR radiation. The survival fraction was determined using a colony-forming assay. The cell cycle progression and apoptosis were detected by flow cytometry (FCM). The expression of the apoptosis-related proteins caspase-3, cleaved-caspase-3, PARP, cleaved-PARP, BAX and Bcl-2 were detected by western blot assay.

RESULTS

After irradiation with 125I seeds CLDR radiation, there was a lower survival fraction, more pronounced cell cycle arrest (G1 arrest and G2/M arrest in A549 and H1299 cells, respectively) and a higher apoptotic ratio for A549 and H1299 cells than after 60Co γ-ray HDR radiation. Moreover, western blot assays revealed that 125I seeds CLDR radiation remarkably up-regulated the expression of Bax, cleaved-caspase-3 and cleaved-PARP proteins and down-regulated the expression of Bcl-2 proteins in A549 and H1299 cells compared with 60Co γ-ray HDR radiation. However, there was little change in the apoptotic ratio and expression of apoptosis-related proteins in normal BEAS-2B cells receiving the same treatment.

CONCLUSIONS

125I seeds CLDR radiation led to remarkable growth inhibition of A549 and H1299 cells compared with 60Co HDR γ-ray radiation; A549 cells were the most sensitive to radiation, followed by H1299 cells. In contrast, normal BEAS-2B cells were relatively radio-resistant. The imbalance of the Bcl-2/Bax ratio and the activation of caspase-3 and PARP proteins might play a key role in the anti-proliferative effects induced by 125I seeds CLDR radiation, although other possibilities have not been excluded and will be investigated in future studies.

摘要

目的

比较¹²⁵I粒子连续低剂量率(CLDR)辐射与⁶⁰Coγ射线高剂量率(HDR)辐射对非小细胞肺癌(NSCLC)细胞的生物学效应。

材料与方法

将A549、H1299和BEAS-2B细胞暴露于¹²⁵I粒子CLDR辐射或⁶⁰Coγ射线HDR辐射。采用集落形成试验测定存活分数。通过流式细胞术(FCM)检测细胞周期进程和凋亡情况。采用蛋白质免疫印迹法检测凋亡相关蛋白caspase-3、裂解的caspase-3、PARP、裂解的PARP、BAX和Bcl-2的表达。

结果

¹²⁵I粒子CLDR辐射后,与⁶⁰Coγ射线HDR辐射相比,A549和H1299细胞的存活分数更低,细胞周期阻滞更明显(A549和H1299细胞分别为G1期阻滞和G2/M期阻滞),凋亡率更高。此外,蛋白质免疫印迹分析显示与⁶⁰Coγ射线HDR辐射相比,¹²⁵I粒子CLDR辐射显著上调了A549和H1299细胞中Bax、裂解的caspase-3和裂解的PARP蛋白的表达,下调了Bcl-2蛋白的表达。然而,接受相同处理的正常BEAS-2B细胞的凋亡率和凋亡相关蛋白的表达几乎没有变化。

结论

与⁶⁰Co HDRγ射线辐射相比,¹²⁵I粒子CLDR辐射对A549和H1299细胞具有显著的生长抑制作用;A549细胞对辐射最敏感,其次是H1299细胞。相比之下,正常BEAS-2B细胞相对抗辐射。Bcl-2/Bax比值的失衡以及caspase-3和PARP蛋白 的激活可能在¹²⁵I粒子CLDR辐射诱导的抗增殖效应中起关键作用,尽管其他可能性尚未排除,将在未来研究中进行调查。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f284/4534329/cae6741cb42b/pone.0133728.g001.jpg

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