基因转染结合局部照射对体内黑色素瘤的抑制作用 :肿瘤的基因—放射治疗策略(英文)  

GROWTH INHIBITION OF MELANOMA IN VIVO BY COMBINING ONCOSTATIN M GENE TRANSFECTION WITH LOCALIZED RADIATION: A GENE-RADIOTHERAPY STRATEGY FOR TUMOR

作　　者：吕星[1] 邢瑞云[1] 裴雪涛[1] 路萍[1] 孙志贤[1] 吴祖泽[1] 

机构地区：[1]军事医学科学院放射医学研究所,北京100850

出　　处：《辐射研究与辐射工艺学报》2001年第2期127-132,共6页Journal of Radiation Research and Radiation Processing

基　　金：国家自然科学基金 (396 70 82 5)资助

摘　　要：探讨OSM对黑色素瘤体内生长的抑制作用及其在基因 -放射治疗中的应用。将人OSMcDNA插入 pCI-neo构成OSM表达质粒 ( pO) ;Egr- 1基因调控序列 (Egr - 1R)连接于OSMcDNA上游构成辐射诱导性OSM表达质粒 ( pEO)。pO和 pEO转染小鼠B1 6黑色素瘤细胞 ,筛选出OSM表达细胞 ( pO - 1 7和 pEO - 1 ) ,皮下接种C5 7小鼠 ,观察和比较相同生长期内瘤体重量及给予60 Coγ射线局部照射后肿瘤抑制率的变化。结果表明 ;在未照射实验中 ,pO - 1 7和 pEO - 1细胞接种 2 0d后的瘤体重量较对照组明显降低 ;在照射实验中 ,pEO- 1细胞照射后 7d瘤体重量的下降最为显著 ,肿瘤抑制率较未照射时提高 42 3%。说明转基困分泌的OSM可对瘤细胞的体内生长产生抑制 ;γ射线可通过Egr - 1R增强OSM表达的途径 ,加剧对肿瘤的抑制 ,体现出基因The study was done to study was done to investigate the inhibitory role of oncostatin M (OSM) on the melanoma growth as well as the potential application of OSM in the gene-radiotherapy for melanoma in vivo. The human OSM cDNA was inserted into the EcoR I-Xba I site of the vector pCI-neo to form the OSM expression vector (pO). The radiation-inducible OSM expression vector (pEO) was constructed by substituting the CMV promoter in pCI-neo with the regulatory sequence of Egr-1 gene (Egr-1R). The constructs pO and pEO were transfected into mouse B-16 melanoma cells, respectively, and then the OSM secreting cells (pO17 and pEO-1) were selected by anti-h OSM antibldy. An investigation on the tumor weight and comparisons of the inhibition rates between irradiated and non-irradiated tumors were taken. Results showed that the in vivo tumor weights of pO17 and pEO-1 cells were drastically reduced compared to either B-16 or B-neo cells as controls in the same period of twenty days after cells had been inoculated subcustaneously into C57BL/6 mice. It was further observed that for pEO-1 cells, but not for pO-17, there was an increase of 42.3% in the inhibition rate of tumor when tumors were treated with 20Gy of \+\{60\}Co γ ray radiation. Firstly, the in vivo growth of tumor could be controlled by OSM secreted from OSM gene-modified cells. Secondarily Egr-1R sequence linked upstream to OSM gene could be activated by irradiation and enhance the expression of OSM, and thereby impose an aggravated damage on tumors in vivo , i.e. a gene-radiotherapy effect.

关 键 词：黑色素瘤 抑瘤蛋白M 基因-放射治疗 基因转染结合部照射 肿瘤 OSM 

分 类 号：R730.55[医药卫生—肿瘤] R739.5[医药卫生—临床医学]