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放射线联合p53基因及内皮抑素治疗小鼠前列腺癌皮下移植瘤
  • ISSN号:0254-5098
  • 期刊名称:《中华放射医学与防护杂志》
  • 时间:0
  • 分类:R378.2[医药卫生—病原生物学;医药卫生—基础医学] R734.2[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]北京大学第一医院放射治疗科,北京100034, [2]北京大学临床肿瘤学院北京肿瘤医院暨北京市肿瘤防治研究所乳腺内科、恶性肿瘤发病机制及转化研究教育部重点实验室
  • 相关基金:国家自然科学基金(30670619)
中文摘要:

目的观察放射线联合p53基因及内皮抑素治疗C57BL/6小鼠前列腺癌皮下移植瘤的效果,并初步探讨其作用机制。方法建立C57BL/6小鼠前列腺癌皮下移植瘤模型。随机分成5组:空白组(A)、放射组(B)、放射线联合p53基因组(c)、放射线联合内皮抑素组(D)及放射线联合p53基因和内皮抑素组(E)。第1天c、E组瘤内注射p53基因腺病毒(1×10^10vp),第1-14天D、E组每日1次腹腔注射内皮抑素(1.5mg/kg)。第4天B、c、D、E组小鼠肿瘤区单次照射(6MVX线DT15Gy)。每日测量肿瘤体积;检测各组肿瘤标本P53、Ki67及血管内皮生长因子(VEGF)的表达及微血管密度值(MVD)。结果4个治疗组的肿瘤生长速度均低于空白组(P=0.000),其中E组生长最慢(P〈0.05)。免疫组织化学结果:4个治疗组P53的表达均明显低于空白组(P=0.000);4个治疗组Ki67的表达均高于空白组,但变化趋势不同:B、c组Ki67的表达值接近,均随时间的推移而逐渐升高(P=0.000),D、E组的表达则呈现波动性;第5天时E组VEGF的表达最低(P〈0.05);肿瘤生长过程中各组MVD值均持续升高,c、D、E3组MVD值在各时间均高于空白组(P〈0.05)。结论放射线联合p53基因及内皮抑素的抑瘤效果优于单独放射治疗及放射线联合p53基因或内皮抑素。三者均有自己的作用机制,但相互之间可以互相影响。

英文摘要:

Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rhendostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1×10^10vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo ( P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P 〈 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 〉 0.05)and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P 〈 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest ( P 〈 0.05). An increased expression of MVD compared ~th the control was shown, and MVD in groups C, D and E were always higher than that in the control ( P 〈 0.05 ). Conclusions The limitation of radiotherapy could be overcome by combination with both p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and end

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期刊信息
  • 《中华放射医学与防护杂志》
  • 北大核心期刊(2011版)
  • 主管单位:中国科学技术协会
  • 主办单位:中华医学会
  • 主编:
  • 地址:北京市德外新康街2号
  • 邮编:100088
  • 邮箱:cjrmp@cjrmp.sina.net
  • 电话:010-62389620
  • 国际标准刊号:ISSN:0254-5098
  • 国内统一刊号:ISSN:11-2271/R
  • 邮发代号:18-93
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:11741