纳米氧化铈颗粒对人肺腺癌耐顺铂细胞辐射敏感性的影响

doi:10.3969/j.issn.1004-616x.2019.06.009

癌变·畸变·突变 ›› 2019, Vol. 31 ›› Issue (6): 464-468.doi: 10.3969/j.issn.1004-616x.2019.06.009

纳米氧化铈颗粒对人肺腺癌耐顺铂细胞辐射敏感性的影响

王春燕, 佟鹏, 李辰, 邵帅, 曲功霖, 苟巧, 王成芳, 齐雪松

中国疾病预防控制中心辐射防护与核安全医学所, 辐射防护与核安全应急中国疾病预防控制中心重点实验室, 北京 100088

收稿日期:2019-06-04 修回日期:2019-11-19 出版日期:2019-11-30 发布日期:2019-12-04
通讯作者: 齐雪松,E-mail:cedar121@sina.com E-mail:cedar121@sina.com
作者简介:王春燕,E-mail:chy5697@163.com。

Effect of cerium oxide nanoparticles on radiosensitivity of a drug-resistant human lung adenocarcinoma cell line

WANG Chunyan, TONG Peng, LI Chen, SHAO Shuai, QU Gonglin, GOU Qiao, WANG Chengfang, QI Xuesong

Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China

Received:2019-06-04 Revised:2019-11-19 Online:2019-11-30 Published:2019-12-04

摘要/Abstract

摘要： 目的：研究纳米氧化铈颗粒对人肺腺癌耐顺铂细胞（A549/DDP）辐射敏感性的影响。方法：采用细胞增殖抑制实验确定γ射线半数抑制剂量和纳米氧化铈的使用浓度，细胞集落形成实验检测γ射线和纳米氧化铈处理后的细胞存活情况。将细胞分为阴性对照，γ射线照射组，纳米氧化铈低、中、高浓度组（分别加入0.000 5、0.05和5 μmol/L的纳米氧化铈处理后，再进行照射），采用流式细胞术进行细胞凋亡率、细胞周期和胞内pH值检测。结果：通过细胞增殖抑制实验，确定γ射线诱导A549/DDP细胞半数抑制剂量为25 Gy。细胞集落形成实验观察发现，与照射组相比，纳米氧化铈低浓度组细胞的SF₂降低、a/b比值和增敏比升高。流式细胞术检测发现，纳米氧化铈低浓度组细胞凋亡率增加（t=5.42，P < 0.05）；纳米氧化铈低、中、高浓度组的S期阻滞明显（t=3.14、4.08、6.81，P < 0.05）；纳米氧化铈低、高浓度组的胞内pH值升高（t=2.86、4.93，P < 0.05）。结论：低浓度纳米氧化铈对于体外培养的A549/DDP细胞具有一定的辐射增敏作用。

关键词: 纳米氧化铈颗粒, A549/DDP细胞, 辐射敏感性, γ射线

Abstract: OBJECTIVE: To study the effect of cerium oxide nanoparticles (CeO₂) on radiosensitivity of A549/DDP. METHODS: The half maximal inhibitory exposure dose and concentration of CeO₂ were determined by inhibitory rate of proliferation of A549/DDP. The cell colony-forming experiment was performed to observe changes of cellular surviving fractions between the radiation group after treated with different concentration of CeO₂ groups and radiation only group. A549/DDP cells were grouped as negative control(control),radiation control (rad),and the low,medium and high concentration of CeO₂ groups (final concentrations were 0.000 5,0.05 and 5 μmol/L). Apoptosis,cell cycle and intracellular pH were determined using by flow cytometry. RESULTS: The half maximal inhibitory exposure dose of A549/DDP induced by γ-rays was 25 Gy,which was determined by inhibitory rate of A549/DDP proliferation. At the survival fraction of 2 Gy (SF₂),the ratios of a/b and the sensitive enhancement ratios (SER) were obtained by the cell colony-forming experiment. Comparing with the rad group,the value SF₂ of low concentration CeO₂ group was decreased. The ratio of a/b and the value of SER of the low concentration CeO₂ group were both increased. From the flow cytometry analyses,the percent of apoptosis in the low concentration CeO₂ group was increased (t=5.42,P < 0.05);S-phase arrest of the low,medium and high concentration CeO₂ groups were obvious (t=3.14,4.08,6.81,P < 0.05). The value of pH in cells of the low and high concentration CeO₂ groups were raised (t=2.86,4.93,P < 0.05). CONCLUSION: All the results indicate that low concentrations of CeO₂ enhanced radiosensitivity of A549/DDP.

Key words: cerium oxide nanoparticles, A549/DDP, radiosensitivity, γ-rays

中图分类号:

R146

王春燕, 佟鹏, 李辰, 邵帅, 曲功霖, 苟巧, 王成芳, 齐雪松. 纳米氧化铈颗粒对人肺腺癌耐顺铂细胞辐射敏感性的影响[J]. 癌变·畸变·突变, 2019, 31(6): 464-468.

WANG Chunyan, TONG Peng, LI Chen, SHAO Shuai, QU Gonglin, GOU Qiao, WANG Chengfang, QI Xuesong. Effect of cerium oxide nanoparticles on radiosensitivity of a drug-resistant human lung adenocarcinoma cell line[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(6): 464-468.

参考文献

[1] 国家癌症中心. 2017中国肿瘤登记年报[M]. 北京:人民卫生出版社, 2018:7.;
[2] 李香兰, 常金, 刘珊珊, 等. 人肺腺癌细胞A549的耐药性与放射敏感性的相关性研究[J]. 中国老年学杂志, 2008, 28(24):2438-2440.;
[3] 杨立娜. 非小细胞肺癌对¹²C⁶⁺重离子的辐射敏感性及其分子细胞生物学机制[D]. 兰州:兰州大学, 2016.;
[4] 陈雪琴, 马胜林, 牟翰舟, 等. 热疗联合放化疗对人肺腺癌耐药细胞株A549/DDP的协同杀伤作用[J]. 中华物理医学与康复杂志, 2008, 30(2):88-91.;
[5] 李士猛, 刘瑾. 甘氨双唑钠对Ⅲ期非小细胞肺癌放疗增敏的临床观察[J]. 肿瘤基础与临床, 2016, 29(5):393-395.;
[6] 陈健, 吴楠. 世界稀土资源现状分析与我国稀土资源可持续发展对策[J]. 农业现代化研究, 2012, 33(1):74-77.;
[7] WASON M S, COLON J, DAS S, et al. Sensitization of pancreatic cancer cells to radiation by cerium oxide nanoparticle-induced ROS production[J]. Nanomed-Nanotechnol Biol Med, 2013, 9(4):558-569.;
[8] SHIN S W, JUNG W, CHOI C, et al. Fucoidan-manganese dioxide nanoparticles potentiate radiation therapy by Co-targeting tumor hypoxia and angiogenesis[J]. Mar Drugs, 2018, 16(12):E510.;
[9] KUNOH T, SHIMURA T, KASAI T, et al. Use of DNA-generated gold nanoparticles to radiosensitize and eradicate radioresistant glioma stem cells[J]. Nanotechnology, 2019, 30(5):055101.;
[10] LIU Z J, TAN H Y, ZHANG X H, et al. Enhancement of radiotherapy efficacy by silver nanoparticles in hypoxic glioma cells[J]. Artif Cells Nanomed Biotechnol, 2018, 46(Sup 3):S922-S930.;
[11] ZHANG X H, LIU Z J, LOU Z C, et al. Radiosensitivity enhancement of Fe₃O₄@Ag nanoparticles on human glioblastoma cells[J]. Artif Cells Nanomed Biotechnol, 2018, 46(Sup 1):975-984.;
[12] YAMAGUCHI H, HAYAMA K, SASAGAWA I, et al. HER2-targeted multifunctional silica nanoparticles specifically enhance the radiosensitivity of HER2-overexpressing breast cancer cells[J]. Int J Mol Sci, 2018, 19(3):E908.;
[13] BRIGGS A, CORDE S, OKTARIA S, et al. Cerium oxide nanoparticles:influence of the high-Z component revealed on radioresistant 9L cell survival under X-ray irradiation[J]. Nanomed-Nanotechnol Biol Med, 2013, 9(7):1098-1105.;
[14] 雷婉婷, 王静萱. 肿瘤微环境在肿瘤细胞有氧糖酵解中的作用[J]. 实用肿瘤学杂志, 2018, 32(2):189-192.;
[15] 潘雅娜, 王雪, 罗清. 肿瘤微环境影响肿瘤多药耐药的研究进展[J]. 重庆医学, 2018, 47(4):555-558.;
[16] SINGH S. Cerium oxide based nanozymes:Redox phenomenon at biointerfaces[J]. Biointerphases, 2016, 11(4):04B202.;
[17] 李宏. 纳米氧化铈的合成修饰及其在辐射防护与肿瘤光动力学治疗中的应用研究[D]. 重庆:第三军医大学, 2017.

纳米氧化铈颗粒对人肺腺癌耐顺铂细胞辐射敏感性的影响

Effect of cerium oxide nanoparticles on radiosensitivity of a drug-resistant human lung adenocarcinoma cell line

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 13

编辑推荐

Metrics

本文评价

[1]	齐雪松, 王春燕, 李辰, 佟鹏, 邵帅, 曲功霖, 苟巧, 苏旭. γ射线对小鼠胸腺淋巴细胞微丝形态及丝切蛋白磷酸化的影响[J]. 癌变·畸变·突变, 2018, 30(4): 249-253,257.
[2]	丁立新, 赵现哲, 姜晓燕, 丁库克. 宫颈癌辐射敏感性相关基因的研究进展[J]. 癌变·畸变·突变, 2017, 29(5): 394-396,401.
[3]	孙鸽, 秦秀军, 王永丽, 李建国, 周朝东, 安全, 闻建华. ⁶⁰Co γ射线对雄性比格犬睾酮分泌及睾丸组织病理学的影响[J]. 癌变·畸变·突变, 2016, 28(6): 443-445,452.
[4]	陈雪,刘建香. miR-34家族在肿瘤及辐射损伤中的研究进展[J]. 癌变·畸变·突变, 2013, 25(1): 76-78.
[5]	张伟，秦秀军，许超琪，李炜宾，尹晶晶，袁慧，李建国. γ射线照后不同时间点人肝细胞基因差异表达谱的研究[J]. , 2011, 23(6): 416-420.
[6]	王卉，封江彬，陆雪，张德钦，张庆召，高玲，陈德清，刘青杰. 60Co γ射线诱导人淋巴细胞线粒体COX II 基因表达改变的研究[J]. , 2011, 23(6): 437-441.
[7]	齐雪松，王春燕，郝述霞，苟巧，佟鹏，苏旭. γ射线诱导小鼠胸腺淋巴细胞中 Arp2、 Arp3和cofilin 基因表达的变化[J]. , 2011, 23(6): 421-424.
[8]	薛振伟，周小林，崔梅萍. γ射线辐照对BEP2D细胞蛋白质组的影响[J]. , 2011, 23(6): 425-428.
[9]	王　卉,李玉文,封江彬,陆　雪,范　莉,陈德清,赵　骅,刘青杰. 60Co γ射线诱导人淋巴细胞GDF15mRNA表达水平的变化[J]. , 2010, 22(5): 352-355.
[10]	安　静;隋建丽;徐勤枝;周平坤. siRNA抑制DNA-PKcs表达及对HeLa细胞增殖的影响[J]. , 2005, 17(6): 327-331.
[11]	吴丛梅;黄天华;谢庆东;李德锐;陈秀如;吴德生;徐小虎. 重组质粒pEgr-P１6在Ec9706细胞中的辐射诱导凋亡作用[J]. , 2004, 16(3): 129-131.
[12]	刘建香;苏　旭. 电离辐射调控脂质体介导的TNFα基因在HeLa细胞中的表达[J]. , 2004, 16(2): 89-91.
[13]	吴丛梅1,黄天华1，吴德生,谢庆东1 ,徐小虎2. pEgr-P16重组质粒的构建及其在EC9706细胞中的辐射诱导表达[J]. , 2003, 15(4): 203-204.