低剂量辐射联合阿霉素对荷乳腺癌裸鼠移植瘤生长及其移植瘤组织中HIF-1α和VEGF表达的影响

doi:10.13481/j.1671-587x.20150109

吉林大学学报(医学版) ›› 2015, Vol. 41 ›› Issue (01): 44-47.doi: 10.13481/j.1671-587x.20150109

低剂量辐射联合阿霉素对荷乳腺癌裸鼠移植瘤生长及其移植瘤组织中HIF-1α和VEGF表达的影响

洪亚琼¹, 鄢鸿¹, 潘润铎², 陈海燕³, 唐文娟⁴, 姜宏宇¹

1. 吉林大学第一医院体检中心, 吉林长春 130021;
2. 吉林大学第一医院放射线科, 吉林长春 130021;
3. 吉林大学第一医院老年干部科, 吉林长春 130021;
4. 一汽集团总医院老年病科, 吉林长春 130011

收稿日期:2014-08-05 发布日期:2015-01-30
通讯作者: 姜宏宇,教授,硕士研究生导师(Tel:0431-88782131,E-mail:jiang_hy@jlu.edu.cn) E-mail:jiang_hy@jlu.edu.cn
作者简介:洪亚琼(1989-),女,福建省南安市人,在读医学硕士,主要从事老年心血管疾病及肿瘤治疗方面的研究。
基金资助:
国家自然科学基金资助课题(81272471);吉林省科技厅自然科学基金资助课题(201115066)

Effects of low-dose radiation combined with adriamycin on growth of transplantation tumor cells,HIF-1α and VEGF expressions in transplantation tumor tissue of breast cancer-bearing nude mice

HONG Yaqiong¹, YAN Hong¹, PAN Runduo², CHEN Haiyan³, TANG Wenjuan⁴, JIANG Hongyu¹

1. Physical Examination Center, First Hospital, Jilin University, Changchun 130021, China;
2. Department of Radiology, First Hospital, Jilin University, Changchun 130021, China;
3. Department of Gerontology, First Hospital, Jilin University, Changchun 130021, China;
4. Department of Gerontology, FAW General Hospital, Changchun 130011, China

Received:2014-08-05 Published:2015-01-30

摘要/Abstract

摘要：

目的: 探讨低剂量辐射(LDR)联合阿霉素(ADM)对荷乳腺癌裸鼠移植瘤生长及移植瘤组织缺氧诱导因子1α(HIF-1α)和血管内皮生长因子(VEGF)表达的影响,阐明LDR联合ADM增强机体抗肿瘤作用的机制。方法: 24只荷乳腺癌裸鼠随机分为假照组(0 mGy)、LDR组(75 mGy)、ADM组和LDR-6h-ADM组(LDR后6h给予ADM),各组荷瘤裸鼠以不同方式处理4 d后全部处死,测量各组小鼠瘤质量,计算抑瘤率,光镜下观察肿瘤组织形态学表现,应用免疫组织化学方法检测肿瘤组织中HIF-1α和VEGF表达。结果: 与假照组比较,其余各组小鼠平均瘤质量均明显降低(P<0.05),LDR-6h-ADM组小鼠平均瘤质量最低,但与LDR组和ADM组比较差异无统计学意义(P>0.05);LDR-6h-ADM组小鼠抑瘤率显著高于ADM组和LDR组(P<0.05)。组织形态学观察,各组小鼠肿瘤组织均见癌细胞分布,LDR-6h-ADM组可见癌细胞片状坏死,癌组织间质疏松,癌细胞坏死程度较ADM组和LDR组明显。免疫组织化学,假照组VEGF和HIF-1α蛋白表达水平最高,LDR-6h-ADM组最低。与假照组比较,其余各组小鼠肿瘤组织HIF-1α和VEGF平均灰度值明显升高,即蛋白表达水平明显降低(P<0.05)。结论: LDR联合ADM可使机体抗肿瘤作用增强,可能与LDR降低肿瘤组织HIF-1α和VEGF的表达、改善肿瘤缺氧及抑制肿瘤血管生成有关。

关键词: 低剂量辐射, 阿霉素, 乳腺肿瘤, 移植瘤, 乏氧诱导因子1&alpha, 血管内皮生长因子

Abstract:

Objective To study the effects of low-dose radiation (LDR) combined with adriamycin(ADM) on the growth of transplantation tumor cells, hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) expressions in transplantation tumor tissue of breast cancer-bearing nude mice, and to clarify the mechanism of enhancing anti-tumor effect of LDR combined with ADM. Methods Twenty-four breast cancer-bearing nude mice were divided into sham irradiation group(0 mGy), LDR group(75 mGy), ADM group and LDR-6h-ADM group (administed with ADM 6 h after LDR).The tumor weight was measured, the inhibitory rate of tumor was calculated, the morphology of tumor tissue was observed by light microscope, and the HIF-1α and VEGF expressions were detected with immunohistochemistry method. Results Compared with sham irradiation group, the mean tumor weights of the mice in other groups were decreased apparently(P<0.05). The mean tumor weight of the mice in LDR-6h-ADM group was the lowest, but had no significant differences when compared with LDR group and ADM group (P>0.05).The inhibitory rate of tumor of the mice in LDR-6h-ADM group was significantly higher than those in ADM group and LDR group (P<0.05).The pathological results showed that the cancer cells could be seen in each group, necrosis of cancer cells could be seen in LDR-6h-ADM group, the cancer tissue's interstitial was loose, and its extent of necrosis in cancer cells was significant compared with ADM and LDR groups.Compared with sham irradiation group, the mean gray values of HTF-1α and VEGF expressions in tumor tissue of mice were increased apparently in other groups (P<0.05). Conclusion LDR combined with ADM can enhance the body's anti-tumor effect, and the effect may be related to reducing the expressions of HIF-1α and VEGF, improving the hypoxia of tumor and inhibiting the formation of tumor angiogenesis.

Key words: low-dose radiation, adriamycin, breast neoplasms, transplantation tumor, hypoxia-inducible factor-1 alpha, vascular endothelial growth factor

中图分类号:

R730.58

洪亚琼, 鄢鸿, 潘润铎, 陈海燕, 唐文娟, 姜宏宇. 低剂量辐射联合阿霉素对荷乳腺癌裸鼠移植瘤生长及其移植瘤组织中HIF-1α和VEGF表达的影响[J]. 吉林大学学报(医学版), 2015, 41(01): 44-47.

HONG Yaqiong, YAN Hong, PAN Runduo, CHEN Haiyan, TANG Wenjuan, JIANG Hongyu. Effects of low-dose radiation combined with adriamycin on growth of transplantation tumor cells,HIF-1α and VEGF expressions in transplantation tumor tissue of breast cancer-bearing nude mice[J]. Journal of Jilin University Medicine Edition, 2015, 41(01): 44-47.

参考文献

[1] 刘小艳,许新华.乏氧微环境与肿瘤治疗抗拒 [J].广东医学,2013,34(23): 3667-3669.

[2] 秦姣,龙汉安.缺氧诱导因子-1α 与肿瘤关系的研究进展 [J].西部医学,2010,22(7): 1323-1325.

[3] 龚晓燕,保永亮,黄金玲.血管内皮生长因子与肿瘤侵袭转移 [J].安徽医药,2013,17(1): 3-5.

[4] Yu H,Sun W,Liu N.The effect of low-dose total body irradiation on tumor-inhibition and signal transduction in tumor tissues of mice bearing S180 sarcoma [J]. Chinese-German J Clin Oncol,2011,10(10): 602-605.

[5] 王畅,王冠军,谭业辉,等.低剂量辐射增强大剂量辐射对人胶质瘤的抑瘤作用 [J].中华放射医学与防护杂志,2008,28(3):221-224.

[6] 陈玉丙,傅海青.低剂量 X 射线对荷瘤小鼠局部大剂量照射抑瘤作用的影响 [J].白求恩医科大学学报,1998,24(6): 568-570.

[7] Cheda A,Nowosielska EM,Wrembel-Wargocka J,et al.Production of cytokines by peritoneal macrophages and splenocytes after exposures of mice to low doses of X-rays [J].Radiat Environ Biophys,2008,47(2): 275-283.

[8] 张忠新,刘建功,刘红艳,等.低剂量电离辐射生物效应研究 [J].辐射研究与辐射工艺学报,2013,31(5):1-6.

[9] 李坤,李小娟,王海军,等.阳江天然放射性高本底地区居民血清免疫学调查研究 [J].中国预防医学杂志,2013,14(10):774-778.

[10] Yu H,Liu N,Wang H,et al.Different responses of tumor and normal cells to low-dose radiation [J].Contemp Oncol (Pozn),2013,17(4): 356-362.

[11] 于洪升,费从合,沈方臻,等.低剂量辐射联合环磷酰胺对肿瘤细胞凋亡、细胞周期以及骨髓增殖的影响 [J].中华放射医学与防护杂志,2004,24(2): 117-119.

[12] Bos R,Zhong H,Hanrahan CF,et al.Levels of hypoxia-inducible factor-1α during breast carcinogenesis [J].J Natl Cancer Inst,2001,93(4): 309-314.

[13] Simiantonaki N,Taxeidis M,Jayasinghe C,et al.Hypoxia-inducible factor 1 alpha expression increases during colorectal carcinogenesis and tumor progression [J].BMC cancer,2008,8(1): 320.

[14] 李福宝,于洪升.低剂量辐射对荷 S180 肉瘤小鼠肿瘤组织 HIF-1α 和 P53 表达的影响 [J].齐鲁医学杂志,2009,24(3): 189-191.

[15] 龚晓燕,保永亮,黄金玲.血管内皮生长因子与肿瘤侵袭转移 [J].安徽医药,2013,17(1): 3-5.

[16] 鞠波,于洪升,郝培.低剂量辐射对小鼠 S180 肉瘤组织 EPO 和 VEGF 表达影响 [J].齐鲁医学杂志,2009,24(4): 315-316.

低剂量辐射联合阿霉素对荷乳腺癌裸鼠移植瘤生长及其移植瘤组织中HIF-1α和VEGF表达的影响

Effects of low-dose radiation combined with adriamycin on growth of transplantation tumor cells,HIF-1α and VEGF expressions in transplantation tumor tissue of breast cancer-bearing nude mice

RichHTML

PDF (PC)

赞

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	于秀艳, 张晓伟, 丛占杰, 李铤, 吴雪峰. 乳腺癌患者血清中hMAM和CD147水平检测及其临床意义[J]. 吉林大学学报(医学版), 2018, 44(06): 1269-1274.
[2]	郑芳, 欧阳征仁, 欧阳靖霖, 周诗力, 罗文. 乳腺癌患者超声图像特征与人类上皮生长因子受体2和Ki-67阳性表达的关联性分析[J]. 吉林大学学报(医学版), 2018, 44(05): 1073-1077.
[3]	于雷, 唐庚, 方芳, 李鑫, 龚守良, 王志成, 王剑锋. 低剂量辐射诱导小鼠睾丸细胞中IRE1α和XBP1 mRNA及其蛋白的表达[J]. 吉林大学学报(医学版), 2018, 44(05): 919-923.
[4]	楚爱景, 程旭锋, 赵慧朵, 王丰莲. 柴芍乳癖颗粒对乳腺增生模型大鼠血清激素水平和乳腺组织中VEGF和bFGF蛋白表达水平的影响及其意义[J]. 吉林大学学报(医学版), 2018, 44(05): 1005-1009.
[5]	郑燕, 王娜, 吴命坤, 刘静乔, 孟亚丽. 米非司酮对稽留流产患者血清和绒毛组织中Ang-1、Ang-2、VEGF、TNF-α和IL-6表达水平的影响[J]. 吉林大学学报(医学版), 2018, 44(04): 791-795.
[6]	李晓, 邱香, 马振卉, 田亚萍. 皮肤转移癌伴发带状疱疹1例报告并文献复习[J]. 吉林大学学报(医学版), 2018, 44(04): 825-827.
[7]	周刘祥, 林琳, 胡鑫敏, 王晓春. 内分泌腺性血管内皮生长因子对结肠癌LoVo细胞增殖和迁移的促进作用[J]. 吉林大学学报(医学版), 2018, 44(03): 516-520.
[8]	何欣, 杨婷婷, 高阳阳, 宋艳秋. 乳腺癌患者心理韧性及其心理干预方式的研究进展[J]. 吉林大学学报(医学版), 2018, 44(02): 455-460.
[9]	于云鹤, 杜烨, 韩冰, 李嗣杰, 宋乐连, 范志民. 新辅助化疗对Luminal B型乳腺癌各亚组的疗效观察及预后分析[J]. 吉林大学学报(医学版), 2018, 44(02): 356-362.
[10]	马鸿云, 庄新明, 许维国, 刘一. 载阿霉素和顺铂的透明质酸纳米粒子对小鼠移植性乳腺癌的抑制作用[J]. 吉林大学学报(医学版), 2018, 44(02): 243-248.
[11]	李小霞, 孙艳, 曲荣锋, 任立参, 李亚荣. 原发性乳腺弥漫大B细胞性淋巴瘤3例报告及文献复习[J]. 吉林大学学报(医学版), 2018, 44(01): 166-169.
[12]	齐亚莉, 刘扬, 梁硕, 龚守良, 王志成, 刘威武. 三重靶向介导的Smac过表达对乳腺癌MDA-MB-231细胞凋亡和周期进程的影响[J]. 吉林大学学报(医学版), 2018, 44(01): 90-94.
[13]	马啸天, 岳小欣, 荣守华, 张玉超, 田远, 石瑛, 李君芳, 贾莉婷. miR-200c对三阴性乳腺癌上皮间质转化的抑制作用及其机制[J]. 吉林大学学报(医学版), 2018, 44(01): 106-110.
[14]	高新雅, 张伟杰, 崔黎, 周学良, 马志俊, 吕转, 池艳艳, 王留兴. TM4SF1在乳腺癌组织中的表达及其临床意义[J]. 吉林大学学报(医学版), 2017, 43(06): 1186-1192.
[15]	牛会坤, 曲洋明, 李美奇, 李璐, 吕欣, 宋媛媛, 高春时, 李波. 新辅助化疗联合卡培他滨治疗乳腺癌疗效和不良反应的Meta分析[J]. 吉林大学学报(医学版), 2017, 43(06): 1171-1176.