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作 者:姜义荣[1] 万得胜[1] 陈万宁[1] 刘扶兴[1] 赖应昌[1] 陈小林[1] 祁妙华[1] 刘春生[2] 陈学良[2] 马道新[2]
机构地区:[1]东莞市人民医院血液科,广东东莞523000 [2]山东大学齐鲁医院血液科,山东济南250031
出 处:《中华肿瘤防治杂志》2006年第13期961-964,共4页Chinese Journal of Cancer Prevention and Treatment
基 金:国家自然科学基金资助(30070321);东莞市科技计划项目资助(200417)
摘 要:目的:探讨双自杀基因CD和TK对K562细胞的体内外抑制作用及前体药物对肿瘤的杀伤作用。方法:将目的基因转染入K562细胞,MTT法观察细胞在体内外的增殖状况及5-FC/GCV对转染细胞的杀伤作用,电子显微镜观察其超微结构变化。将K562/CDgly TK和K562细胞接种于裸鼠皮下,观察各种肿瘤细胞在体内的成瘤情况及对前体药物治疗的敏感性。结果:单独使用GCV或5-FC对K562及K562/CDgly TK细胞产生明显的杀伤作用,联合应用该2种药物对肿瘤细胞的杀伤作用更强。将K562细胞和K562/CDgly TK细胞接种于小鼠皮下后小鼠成瘤率为100%,GCV或5-FC可明显抑制裸鼠体内的肿瘤形成,联合应用GCV和5-FC治疗K562/CDglyTK细胞在小鼠体内形成的肿瘤,较单独应用GCV和5-FC及对照组小鼠形成的肿瘤体积明显缩小,生存期也明显延长。结论:双自杀基因在体内外对K562细胞均有明显的抑制作用,可增加前体药物GCV和5-FC对瘤细胞的杀伤率。OBJECTIVE: To study the killing effect of double suicide genes system on K562 cells in vivo and in vitro. METHODS: CDglyTK gene was transfected into K562 cells by using lipofectamine. K562 cells were infected with vi ral supernant. K562/CDgly TK cells were treated with 5-FC and/or GCV. The mice were divided into three groups randomly: tumor formation group, tumor inhibition group and tumor therapy group. Each mouse was implanted with K562/CDgly TK cells or K562 cells. RESULTS: The killing effect of 5-FC and GCV in combination on K562/CDglyTK was more effective than that of using 5-FC or GCV alone. In vivo study, the rate of tumor formation was 100%. Double suicide genes could suppress tumor formation of K562/CDglyTK cells. After the mice were treated with double suicide genes, the median tumor volume of mice implanted with K562/CDglyTK cells decreased obviously compared with the control group. Their median survival was significantly prolonged. CONCLUSIONS: Double suieide genes are more effective for killing effect on K562 cells in vivo and in vitro. It may be applicable for clinical gene therapy.
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