不同剂量125I粒子植入对人乳腺癌裸鼠荷瘤增殖的抑制作用及其机制

doi:10.13481/j.1671-587x.20190619

吉林大学学报(医学版) ›› 2019, Vol. 45 ›› Issue (06): 1305-1309.doi: 10.13481/j.1671-587x.20190619

不同剂量¹²⁵I粒子植入对人乳腺癌裸鼠荷瘤增殖的抑制作用及其机制

朱中博¹, 钱建升², 杨硕², 李康乐³, 窦建卫³

1. 甘肃中医药大学基础医学院方剂教研室, 甘肃兰州 730000;
2. 西安交通大学第一附属医院放射科, 陕西西安 710061;
3. 西安交通大学医学部药学院, 陕西西安 710061

收稿日期:2018-12-04 出版日期:2019-12-05 发布日期:2019-12-05
通讯作者: 窦建卫,副教授,副主任医师,硕士研究生导师(Tel:029-82657740,E-mail:djw@mail.xjtu.edu.cn) E-mail:djw@mail.xjtu.edu.cn
作者简介:朱中博(1994-),男,甘肃省定西市人,在读医学硕士,主要从事方剂作用机制和药效物质基础方面的研究。
基金资助:
国家自然科学基金资助课题（81873311，81573983）；陕西省科技厅重点研发计划项目资助课题（2017SF109）

Inhibitory effect of different doses of ¹²⁵I seed implantation on tumor-bearing proliferation in nude mice with breast cancer and its mechanism

ZHU Zhongbo¹, QIAN Jiansheng², YANG Shuo², LI Kangle³, DOU Jianwei³

1. Department of Presciption Teaching and Research, School of Basic Medical Sciences, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China;
2. Department of Radiology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China;
3. School of Pharmacy, Faculty of Medical Sciences, Xi'an Jiaotong University, Xi'an 710061, China

Received:2018-12-04 Online:2019-12-05 Published:2019-12-05

摘要/Abstract

摘要： 目的：观察不同剂量¹²⁵I粒子植入对人乳腺癌荷瘤裸鼠的抑瘤作用，探讨其作用机制。方法：选择健康BALB/c裸鼠于第4乳脂肪垫移植人乳腺癌HMLER90hi细胞，建立裸鼠荷瘤模型。将建模成功后的40只小鼠随机分为空白对照组和低、中及高剂量¹²⁵I粒子组，每组10只。空白对照组小鼠仅植入1粒空白粒子（不含放射性元素），低、中和高剂量组小鼠按照巴黎系统原则分别植入放射剂量为1.48×10^-7、2.22×10^-7和2.96×10^-7Bq¹²⁵I粒子。测量各组小鼠肿瘤体积和瘤体质量，计算各组小鼠肿瘤生长抑制率；ELISA法检测各组荷瘤裸鼠肿瘤组织中端粒酶蛋白水平，qRT-PCR法检测各组小鼠HMLER90hi细胞中CD90和粒细胞-巨噬细胞集落刺激因子（GM-CSF） mRNA表达水平。结果：¹²⁵I粒子植入7、14和28 d后，与空白对照组比较，不同剂量¹²⁵I粒子组小鼠肿瘤质量降低（P<0.05或P<0.01），肿瘤体积减小（P<0.05或P<0.01），肿瘤生长抑制率明显升高（P<0.05或P<0.01）；ELISA检测，与空白对照组比较，不同剂量¹²⁵I粒子组小鼠肿瘤组织中端粒酶蛋白水平升高（P<0.05或P<0.01）；qRT-PCR检测，与空白对照组比较，不同剂量¹²⁵I粒子组小鼠HMLER90hi细胞中CD90和GM-CSF mRNA表达水平明显降低（P<0.05或P<0.01）。结论：不同剂量¹²⁵I粒子可抑制乳腺癌裸鼠荷瘤增殖，其作用机制可能与其抑制荷瘤组织中CD90和GM-CSF mRNA表达有关。

关键词: ¹²⁵I粒子, HMLER90hi细胞, 粒细胞-巨噬细胞集落刺激因子, CD90

Abstract: Objective: To observe the anti-tumor effect of different doses of ¹²⁵I seed implantation in the human breast cancer bearing nude mice, and to explore the mechanism. Methods: The healthy BALB/c nude mice were selected,and the human breast cancer HMLER90hi cells were transplanted into the fourth breast fat pad to establish the tumor-bearing models of nude mice. After successful modeling, 40 nude mice were randomly divided into:blank control group and low, middle and high doses of ¹²⁵I particle groups,and there were 10 rats in each group. The mice in blank control group were only implanted with one blank particle (without radioactive elements); the mice in low, middle and high doses of ¹²⁵I particle groups were implanted with 1.48×10^-7, 2.22×10^-7 and 2.96×10^-7 Bq ¹²⁵I particles, respectively, according to the Paris system principle. The volumes and weights of tumor of the mice in various groups were detected,and the inhibitory rates of growth of tumor of the mice in various groups were calculated.The levels of telomerase protein in tumor tissue of the mice in various groups were determined by ELISA method,the expression levels of CD90 and granulocyte-macrophage colony stimulating factor (GM-CSF)mRNAin the HMLER90hi cells of the mice in various groups were detected by qRT-PCR method. Results: At 7, 14 and 28 d after implantation of ¹²⁵I particles, the weights and volumes of tumor of the mice in different doses of ¹²⁵I particle groups were decreased compared with blank control group(P<0.05 or P<0.01), and the inhibitory rates of growth of tumor of the mice were significantly increased (P<0.05 or P<0.01);the ELISA results showed that compared with blank control group, the levels of telomerase protein in tumor tissue of the mice in different doses of ¹²⁵I particle groups were significantly decreased(P<0.05 or P<0.01);the qRT-PCR results showed that compared with blank control group, the expression levels of CD90 and GM-CSF mRNA in the HMLER90hi cells of the mice in different doses of ¹²⁵I particle groups were significantly decreased(P<0.05 or P<0.01). Conclusion: Different doses of ¹²⁵I particles can inhibit the proliferation of breast cancer in the nude mice, and its mechanism may be related to the inhibition of expressions of CD90 and GM-CSF mRNA in tumor-bearing tissue.

Key words: ¹²⁵I particle, HMLER90hi cells, granulocyte-macrophage colony stimulating factor, CD90

中图分类号:

R730.55

朱中博, 钱建升, 杨硕, 李康乐, 窦建卫. 不同剂量¹²⁵I粒子植入对人乳腺癌裸鼠荷瘤增殖的抑制作用及其机制[J]. 吉林大学学报(医学版), 2019, 45(06): 1305-1309.

ZHU Zhongbo, QIAN Jiansheng, YANG Shuo, LI Kangle, DOU Jianwei. Inhibitory effect of different doses of ¹²⁵I seed implantation on tumor-bearing proliferation in nude mice with breast cancer and its mechanism[J]. Journal of Jilin University(Medicine Edition), 2019, 45(06): 1305-1309.

参考文献

[1] SIEGEL RL, MILLER KD, JEMAL A. Cancer Statistics, 2019[J].CAA Cancer J Clin,2019,69(1):7-34.
[2] GINSBURG O, BRAY F, COLEMAN M P, et al. The global burden of women’s cancers: a grand challenge in global health[J]. Lancet, 2017, 389(10071): 847-860.
[3] WEN D, WEN X, YANG Y, et al. Urban rural disparity in female breast cancer incidence rate in China and the increasing trend in parallel with socioeconomic development and urbanization in a rural setting[J]. Thorac Cancer, 2018, 9(2): 262-272.
[4] 方文涛, 谷志涛, 陈克能. 胸腺肿瘤微创手术研究进展[J]. 中国肺癌杂志, 2018, 21(4):269-272.
[5] 刘伟欣, 王淑莲,宋永文, 等. 乳腺导管内原位癌治疗趋势和预后单中心分析[J]. 中华放射肿瘤学杂志, 2019, 28(2):96-101.
[6] 孙文,牛洪欣. 放射性¹²⁵I粒子植入治疗消化道肿瘤的研究进展[J]. 中国微创外科杂志, 2018, 18(9):842-845.
[7] 罗开元. 实用组织间植入内放射治疗恶性肿瘤学[M]. 北京:人民卫生出版社, 2008:9-16.
[8] 夏寿萱.放射生物学[M].北京:军事医学科学出版社,1998:178-218.
[9] 王巧瑜, 潘洁, 周元敏. 经肝动脉化疗栓塞术联合门静脉内¹²⁵I粒子植入治疗原发性肝癌合并门静脉癌栓的效果观察[J]. 临床肝胆病杂志, 2018,34(1):137-141.
[10] 曲昂, 王俊杰, 姜伟娟,等. ¹²⁵I粒子植入挽救性治疗放疗后盆腔复发宫颈癌的疗效分析[J]. 中华核医学与分子影像杂志, 2018, 38(1):17-21.
[11] MORRISON H, MENON G, LAROCQUE M P, et al. Initial evaluation of advanced collapsed cone engine dose calculations in water medium for I-125 seeds and COMS eye plaques[J]. Med Phys, 2018, 45(3):1276-1286.
[12] 王珂, 任予, 陈武科. 恶性肿瘤的放射性粒子植入治疗[J]. 现代肿瘤医学, 2004, 12(5):485-487.
[13] JELENA K, DRENKA T, ALEKSANDRA J, et al. Metabolic plasticity of stem cells and macrophages in cancer[J]. Front Immunol, 2017, 8(8):1-9.
[14] NETEA-MAIER R T, SMIT J W A, NETEA M G. Metabolic changes in tumor cells and tumor-associated macrophages: a mutual relationship[J]. Cancer Lett, 2018, 413: 102-109.
[15] IONESCU L, BYRNE R N, VAN HAAFTEN T, et al. Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action[J]. Am J Physiol Lung Cell Mol Physiol, 2016, 303(11):L967-L977.
[16] GUPTA P B, ONDER T T, JIANG GZ, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening[J]. Cell, 2009, 138(4):645-659.
[17] 窦建卫, 黄芊, 赵天一, 等. 阳和汤对乳腺癌MDA-MB-231细胞NF-κB、IL-8表达的影响[J]. 四川中医, 2017, 35(2):44-47.
[18] 沈伟, 李康乐, 尚荣国, 等.阳和汤对乳腺癌干细胞CD90、IL-8 mRNA表达水平的影响[J]. 四川中医, 2019, 37(3):44-46.
[19] CHO H, SEO Y, LOKE K M, et al. Cancer-stimulated CAFs enhance monocyte differentiation and pro-tumoral TAM activation via IL-6 and GM-CSF secretion[J]. Clin Cancer Res, 2018, 24(21): 5407-5421.
[20] 王正林, 孔繁学, 胡祥. 肿瘤相关巨噬细胞研究进展[J]. 中华实验外科杂志, 2016, 33(2):546-549.
[21] 王守杰,王建莉,蔡志坚. Th17细胞及其在肿瘤免疫中作用的最新进展[J]. 中国肿瘤生物治疗杂志, 2018, 25(3):293-299.
[22] 罗益贤,马捷,刘永光,等.动态增强MRI对乳腺癌新辅助化疗的疗效评价及预测[J].中国医学物理学杂志,2019,36(7):794-799.

不同剂量¹²⁵I粒子植入对人乳腺癌裸鼠荷瘤增殖的抑制作用及其机制

Inhibitory effect of different doses of ¹²⁵I seed implantation on tumor-bearing proliferation in nude mice with breast cancer and its mechanism

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