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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
其他题名Effect of radiation combined with p53 gene therapy and endostatin on mouse prostate cancer
张敏1; 任军1; 徐博1; 高献书1; 何志嵩1; 何晓明1; 张明1; 刘朝兴1; 何新勇1; 曹光明1; 张绍龙1
关键词前列腺癌 基因治疗 P53腺病毒 内皮抑素 放射 Prostate Cancer Genctberapy Rad P53 Endostatin Radiation
刊名中华放射医学与防护杂志
2009
DOI10.3760/cma.j.issn.0254-5098.2009.03.003
29期:3页:259-264
收录类别中国科技核心期刊 ; 中文核心期刊 ; CSCD
文章类型Journal Article
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(1×1010vp),第1-14天D、E组每日1次腹腔注射内皮抑素(1.5 mg/kg).第4天B、C、D、E组小鼠肿瘤区单次照射(6 MV X线DT15 Gy).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、E 3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. 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 rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp 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 with 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 beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.
语种中文
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文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/42296
Collection北京大学第一临床医学院_放射治疗科
作者单位1.北京大学第一医院放射治疗科,100034
2.北京大学临床肿瘤学院、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
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GB/T 7714
张敏,任军,徐博,等. 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[J]. 中华放射医学与防护杂志,2009,29(3):259-264.
APA 张敏.,任军.,徐博.,高献书.,何志嵩.,...&张绍龙.(2009).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.中华放射医学与防护杂志,29(3),259-264.
MLA 张敏,et al."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".中华放射医学与防护杂志 29.3(2009):259-264.
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