[1]霍小东,王慧星,阎卫亮,等.血管内皮抑制素对125I近距离照射裸鼠肺癌移植瘤的增敏效应研究[J].国际放射医学核医学杂志,2016,40(5):357-362.[doi:10.3760/cma.j.issn.1673-4114.2016.05.006]
　Huo Xiaodong,Wang Huixing,Yan Weiliang,et al.Sensitization effect of endostatin for 125I brachytherapy on transplanted tumor in nude mice[J].International Journal of Radiation Medicine and Nuclear Medicine,2016,40(5):357-362.[doi:10.3760/cma.j.issn.1673-4114.2016.05.006]
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血管内皮抑制素对125I近距离照射裸鼠肺癌移植瘤的增敏效应研究(/HTML)
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
40
期数:
2016年第5期
页码:
357-362
栏目:
论著
出版日期:
2016-09-25

文章信息/Info

Title:
Sensitization effect of endostatin for 125I brachytherapy on transplanted tumor in nude mice
作者:
霍小东1;  王慧星2;  阎卫亮1;  焦玲3;  张文艺3;  郑广钧1;  王俊杰4;  于振涛5;  柴树德1
1. 300211, 天津医科大学第二医院胸外科;
2. 300211, 天津医科大学第二医院疼痛科;
3. 300192 天津, 中国医学科学院放射医学研究所, 天津市放射医学与分子核医学重点实验室;
4. 100191, 北京大学第三医院肿瘤治疗中心放疗科;
5. 300060, 天津医科大学附属肿瘤医院食管肿瘤科, 天津市肿瘤防治重点实验室
Author(s):
Huo Xiaodong1;  Wang Huixing2;  Yan Weiliang1;  Jiao Ling3;  Zhang Wenyi3;  Zheng Guangjun1;  Wang Junjie4;  Yu Zhentao5;  Chai Shude1
1. Department of Thoracic Surgery, the Second Hospital of Tianjin Medical University, Tianjin 300211, China;
2. Pain Management Center, the Second Hospital of Tianjin Medical University, Tianjin 300211, China;
3. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China;
4. Department of Radiation Oncology, Peking University Third Hospital, Beijing 100191, China;
5. Tianjin Key Laboratory of Cancer Prevention and Therapy, Department of Esophageal Oncology, Cancer Institute and Hospital of Tianjin Medical University, Tianjin 300060, China
关键词:
内皮抑素类; 肺肿瘤; 辐射增敏药; 近距离放射疗法
Keywords:
Endostatins; Lung neoplasms; Radiation-sensitizing agents; Brachytherapy
DOI:
10.3760/cma.j.issn.1673-4114.2016.05.006
摘要:
目的 探讨重组人血管内皮抑制素对125I粒子植入治疗裸鼠肺癌移植瘤模型的辐射增敏效应。方法 建立裸鼠移植瘤模型，随机分成对照组（A组）、125I植入组（B组）、重组人血管内皮抑制素组（C组）和125I植入联合重组人血管内皮抑制素组（D组），每组20只。移植瘤直径达2 cm时行125I粒子植入，处方剂量20 Gy，采用治疗计划系统计算移植瘤的体积及接受剂量。按每只裸鼠每天给予20 mg/kg重组人血管内皮抑制素，连续给药14 d，观察并记录肿瘤生长的速度和瘤体体积的变化，分别于第15、30天时处死裸鼠，并通过免疫组化方法检测血管内皮生长因子（VEGF）的表达和微血管密度（MVD），通过RT-PCR分别检测各组肿瘤组织中αvβ3 mRNA水平。结果 第15、30天时，D组的重量抑瘤率和体积抑瘤率与B、C组相比明显增加，差异有统计学意义，B组和D组第30天时的重量抑瘤率和体积抑瘤率均较第15天时明显增加，差异有统计学意义。免疫组化结果显示，第15、30天时， D组与A、B、C组VEGF、MVD差异均有统计学意义，其中，C组与A、B组VEGF、MVD差异有统计学意义，C组第30天时的VEGF表达水平和MVD较第15天时增加，差异有统计学意义。RT-PCR结果显示，第15、30天时，与A组相比，B组αvβ3 mRNA的表达有所增加，并随时间的延长增加更明显，差异有统计学意义，而C组和D组αvβ3 mRNA的表达下降，差异有统计学意义。结论 重组人血管内皮抑制素对肺癌移植瘤的近距离辐射增敏作用明确，VEGF、MVD、αvβ3 mRNA的表达变化是其重要机制。
Abstract:
Objective To investigate the radiation sensitization effect of endostatin on transplanted tumors in nude mice with 125I radioactive seed. Methods Mice were randomly assigned to four groups(n=20):control group(group A), 125I radioactive seed group(group B), endostatin group(group C), and 125I radioactive seed combined with endostatin group(group D). When the diameter of the transplanted tumor was greater than 2 cm, 125I radioactive particles were implanted. The prescription dose was 20 Gy. Treatment planning system was used to calculate the target area and size of tumors. Endostatin was injected intraperitoneally at 20 mg/kg once every day for 14 days, and the changes in tumor growth and size were observed. The animals were sacrificed at 15 and 30 days. The expression levels of vascular endothelial growth factor(VEGF) and microvessel density(MVD) in tumor tissues were detected by immunohistochemistry, whereas αvβ3 mRNA levels were determined by RT-PCR. Results Compared with groups B and C, the tumor size, tumor weight, and tumor growth inhibitory rate of group D significantly increased at 15 and 30 days. The tumor size, tumor weight, and tumor growth inhibitory rate of groups B and D significantly increased at 30 days compared with those at 15 days. Immunohistochemical staining revealed that the expression levels of VEGF and MVD in group D were significantly different at 15 and 30 days compared with those in groups A, B, and C. The expression of VEGF and MVD in group C was significantly different at 15 and 30 days compared with that in groups A and B. VEGF and MVD in group C were significantly up-regulated at 30 days compared with those at 15 days. RT-PCR analysis demonstrated that the expression of αvβ3 mRNA in group B obviously increased with time compared with that in group A. Compared with group A, αvβ3 mRNA in group B was up-regulated, whereas αvβ3 mRNA in groups C and D was significantly down-regulated. Compared with groups C and B, group D exhibited a statistically significant difference. Conclusion Endostatin is helpful to brachytherapy of lung tumor with radiosensitizing enhancement effects. Changes in VEGF, MVD, and αvβ3 mRNA may be the rational treatment mechanism.

参考文献/References:

[1] 杨林, 王金万, 汤仲明, 等.重组人血管内皮抑制素Ⅰ期临床研究[J].中国新药杂志, 2004, 13(6):548-553.DOI.10.3969/j.issn.1673-5552.2006.08.036.Yang L, Wang JW, Tang ZM, et al.Human recombinant endostatin Ⅰ period clinical research[J].Chin J New Drugs, 2004, 13(6):548-553.
[2] Yang P, Allen MS, Aubry MC, et al.Clinical features of 5, 628 primary lung cancer patients:experience at Mayo Clinnic from 1997 to 2003[J].Chest, 2005, 128(1):452-462.DOI:10.1378/chest.128.1.452.
[3] Goeckenjan G.Lung cancer-historical development, current status, future prospects[J].Pneumologie, 2010, 64(9):555-559.DOI:10.1055/s-0030-1255636.
[4] Wang T, Nelson RA, Bogardus A, et al.Five-year lung cancer survival:which advanced stage nonsmall cell lung cancer patients attain long-term survival?[J].Cancer, 2010, 116(6):1518-1525.DOI:10.1002/cncr.24871.
[5] 张福君, 李传行, 吴沛宏, 等.125I粒子组织间植入治疗局部晚期肺癌的对比研究.中华医学杂志, 2007, 87(46):3272-3275.DOI:10.3760/j.issn:0376-2491.2007.46.009.Zhang FJ, Li CX, Wu PH, et al.CT guided radioactive 125I seed implantation in treating localized advanced pulmonary carcinoma[J].Natl Med J China, 2007, 87(46):3272-3275.
[6] 霍小东, 郑广钧, 柴树德, 等.CT引导下125I放射性粒子植入治疗Ⅲ期非小细胞肺癌疗效分析[J].中华放射医学与防护杂志, 2012, 32(2):199-203.DOI.10.3760/cma.j.issn.0254-5098.2012.02.023.Huo XD, Zheng GJ, Chai SD, et al.Clinical efficacy of CT-guided 125l radioactive seeds implantation for stage Ⅲ of non-small cell lung cancer[J].Chin J Radiol Med Prot, 2012, 32(2):199-203.
[7] Kim YM, Hwang S, Kim YM, et al.Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1[J].J Biol Chem, 2002, 277(31):27872-27879.DOI:10.1074/jbc.M202771200.
[8] 王金万, 孙燕, 刘永煜, 等.重组人血管内皮抑素联合NP方案治疗晚期NSCLC随机、双盲、对照、多中心Ⅲ期临床研究[J].中国肺癌杂志, 2005, 8(4):283-290.Wang JW, Sun Y, Liu YY, et al.Results of randomized, multicenter, double-blind phase Ⅲ trial of rh-endostatin(YH-16) in treatment of advanced non-small cell lung cancer patients[J].Chin J Lung Cancer, 2005, 8(4):283-290.
[9] Zhang L, Ge W, Hu K, et al.Endostar down-regulates HIF-1 and VEGF expression and enhances the radioresponse to human lung adenocarcinoma cancer cells[J].Mol Biol Rep, 2012, 39(1):89-95.DOI:10.1007/s11033-011-0713-6.
[10] Wen QL, Meng MB, Yang B, et al.Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice[J].Cancer Sci, 2009, 100(8):1510-1519.DOI:10.1111/j.1349-7006.2009.01193.x.
[11] Jiang XD, Dai P, Wu J, et al.Inhibitory effect of radiotherapy combined with weekly endostatin on the human pulmonary adenocarcinoma A549 xenografts in nude mice[J].Lung Cancer, 2011, 72(2):165-171.DOI:10.1016/j.lungcan.2010.09.003.
[12] Meng MB, Jiang XD, Deng L, et al.Enhanced radioresponse with a novel endostatin protein via tumor vasculature remodeling:experimental and clinical evidence[J].Radiother Oncol, 2013, 106(1):130-137.DOI:10.1016/j.radonc.2012.10.022.
[13] You ZY, Zhao Y, Liu F, et al.The radiosensitization effects of Endostar on human lung squamous cancer cells H-520[J/OL].Cancer Cell Int, 2010, 10:17[2016-04-14].http:www.cancerci.com/content/10/1/17.DOI:10.1186/1475-2867-10-17.
[14] Sugihara T, Magae J, Wadhwa R, et al.Dose and dose-rate effects of low-dose ionizing radiation on activation of Trp53 in immortalized murine cells[J].Radiat Res, 2004, 162(3):296-307.
[15] Jain RK.Normalization of tumor vasculature:an emerging concept in antiangiogenic therapy[J].Science, 2005, 307(576):58-62.DOI:10.1126/science.1104819.
[16] Jain RK.Normalizing tumor microenvironment to treat cancer:bench to bedside to biomarkers[J].J Clin Oncol, 2013, 31(17):2205-2218.DOI:10.1200/JCO.2012.46.3653.
[17] Abdollahi A, Griggs DW, Zieher H, et al.Inhibition of αvβ3 integrin survival signaling enhances antiangiogenic and antitumor effects of radiotherapy[J].Clin Cancer Res, 2005, 11(17):6270-6279.DOI:10.1158/1078-0432.CCR-04-1223.
[18] Peng F, Xu Z, Wang J, et al.Recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models[J/OL].PLoS One, 2012, 7(4):e34646[2016-04-14].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322143.DOI:10.1371/journal.pone.0034646.
[19] Liu J, Zhang Y, Sun P, et al.Enhanced therapeutic efficacy of adenovirus-mediated interleukin-24 gene therapy combined with ionizing radiotherapy for nasopharyngeal carcinoma[J].Oncol Rep, 2013, 30(3):1165-1174.DOI:10.3892/or.2013.2550.

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备注/Memo

备注/Memo:
收稿日期:2016-04-14
基金项目:天津市自然科学基金(15JCYBJC28400);天津医科大学科学基金(2014KYQ27)
通讯作者:柴树德,Email:chaishude@126.com
更新日期/Last Update: 1900-01-01