| 张永春,岳麓,尚庆军,姜鹏,于壮.辐射诱导双基因质粒pEgr-1-endostatin-TNF-α的抗肿瘤作用研究[J].中华放射医学与防护杂志,2010,30(4):399-402 |
| 辐射诱导双基因质粒pEgr-1-endostatin-TNF-α的抗肿瘤作用研究 |
| Anti-tumor effect of pEgr-1-endostatin-TNF-α recombinant plasmid expression induced by ionizing radiation |
| 投稿时间：2009-10-30 |
| DOI：10.3760/cma.j.issn.0254-5098.2010.04.006 |
| 中文关键词: 内皮抑素 肿瘤坏死因子 基因放疗 放射疗法 |
| 英文关键词:Endostatin TNF-α Gene-radiotherapy Irradiation |
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| 中文摘要: |
| 目的 探讨放射线诱导重组质粒pEgr-1-endostatin-TNF-α在小鼠体内的表达及其与射线协同抗肿瘤效应。方法 Lewis肺癌荷瘤鼠240只,随机分为4组:对照组、照射组、质粒组、质粒+照射组。将重组质粒pEgr-1-endostatin-TNF-α注射到荷瘤鼠肿瘤内,24 h后对质粒+照射组采用γ射线肿瘤局部照射10 Gy,诱导目的基因表达,ELISA法测定小鼠不同时间血清中的内皮抑素及TNF-α浓度,免疫组织化学染色检测肿瘤组织中血管内皮细胞CD31的表达,与HE染色分别计算肿瘤血管密度,测量肿瘤大小,观察肿瘤生长情况。结果 质粒+照射组内皮抑素及TNF-α表达量明显增加,第2周表达量达到高峰,分别为(52.64±4.19)和(12.01±0.87)ng/ml,持续到第4周仍有较高浓度表达,与其他3组比较差异有统计学意义(F=29.726,P<0.05)。质粒+对照组HE染色肿瘤组织血管密度较对照组明显减少[(4.7±0.8)与(10.0±1.2)个/视野, t=14.063, P<0.05],肿瘤生长较对照组和照射组受到明显抑制[(5907.2±78.6)、(4653.4±32.8)和(763.5±12.3) mm3, F=16.415,P <0.05)]。结论 重组质粒pEgr-1-endostatin-TNF-α可以通过射线的诱导在小鼠体内表达,与单纯放疗相比较表现出明显的抑制肿瘤血管形成和控制肿瘤生长的作用。 |
| 英文摘要: |
| Objective To study the anti-tumor effects of pEgr-1-endostatin-TNF-α gene-radiotherapy on mice bearing Lewis lung carcinoma, and to explore the mechanism involved. Methods 240 mice with Lewis lung carcinoma were randomly divided into four groups, including control group, irradiation group, liposome group, and liposome combined irradiation group. The plasmids packed by liposome were injected locally into the tumors of the mice, and the tumors of liposome combined irradiation group were irradiated with 10 Gy γ-rays 24 h later. The expression levels of TNF-α and endostatin in mouse serum were measured by ELISA. Then the tumor growth rates at different time were observed. Tumor angiogenesis density were estimated on frozen sections stained with CD31 by using the Chalkley counting method to vessel hot-spots. The tumor inhibition rates were also calculated.Results Radiation induced the expression of pEgr-1-endostatin-TNFα. The endostatin and TNF-α were expressed steadily for about 4 weeks. The highest levels of expression of the endostatin and TNF-α were (52.64±4.19)and(12.01±0.87)ng/ml at 2 week. The expression levels of TNF-α and endostatin were higher in combined therapy group than those in other groups(F=29.726,P<0.05). Compared with the control group, the density of tumor angiogenesis were depressed [(4.7±0.8) vs (10.0±1.2)/field, t=14.063, P<0.05]and tumor growth were significantly inhibited compared to the control group and irradiation group [(5907.2±78.6), (4653.4±32.8) and (763.5±12.3) mm3, F=16.415,P<0.05)].Conclusions The expression of pEgr-1-endostatin-TNFα could be induced by irradiation in dose- and time-dependent manner.The effect of antitumor and angiogenesis inhibition may be more significant than irradition. |
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