YCD/5-FC自杀基因治疗系统对K562B白血病细胞杀伤作用的小鼠体内实验研究

来源 :中华血液学杂志 | 被引量 : 0次 | 上传用户:q56260916
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目的 了解酵母菌胞嘧啶脱氨酶 5 氟胞嘧啶 (YCD 5 FC)系统在体内对转基因高致瘤性K5 6 2细胞 (K5 6 2B细胞 )的杀伤效应。方法 以高滴度逆转录病毒转染K5 6 2B细胞并筛选出阳性转染克隆YCD K5 6 2B ;12只SCID小鼠分为治疗及对照组 ,在小鼠左右两侧近前肢处腹部皮下注射YCD K5 6 2B及K5 6 2B细胞 ,成瘤后治疗组腹腔注射 5 0 0mg kg 5 FC共 10d ,对照组腹腔注射生理盐水 ,观察瘤体相对体积变化及病理变化。结果 瘤细胞接种第 2 1天 ,瘤体相对体积分别为 :YCD K5 6 2B +5 FC组 2 .92 2± 0 .5 81,YCD K5 6 2B +生理盐水组 2 4.434± 4.790 ,K5 6 2B +5 FC组 2 2 .70 1± 2 35 0 ,K5 6 2B +生理盐水组 2 4.46 0± 1.6 70 ;YCD K5 6 2B +5 FC组与YCD K5 6 2B +生理盐水组相比差异非常显著 (P =0 0 0 0 1) ,K5 6 2B +5 FC组及K5 6 2B +生理盐水组相比 ,差异无显著性 (P =0 .0 96 ) ,表明 5 FC对转YCD基因的K5 6 2B白血病细胞有明显的杀伤效应 ,而对未转基因细胞的生长无影响 ;YCD K5 6 2B +5 FC组瘤体于瘤细胞接种后第 12~第 15天 (5 FC治疗的第 3~第 6天 )有所缩小 (最小的相对体积为 0 .6 81) ,病理检查可见 5 FC治疗组瘤体有以小动脉血管为中心的坏死。结论 YCD 5 FC系统在体内对转YCD Objective To understand the killing effect of the yeast YCD 5 FC system on transgenic high tumorigenic K5 6 2 cells (K5 6 2B cells) in vivo. Methods K5 6 2B cells were transfected with high titer retrovirus and positive clones YCD K5 6 2B were screened. Twelve SCID mice were divided into treatment group and control group. The animals were injected subcutaneously YCD K5 6 2B and K5 6 2B cells were injected intraperitoneally with 500 mg kg 5 FC for 10 days. The control group was injected with saline intraperitoneally to observe the relative volume change and pathological changes. Results On the 21st day after inoculation of tumor cells, the relative volumes of tumor were respectively 2.92 2 ± 0.51 in YCD K5 6 2B +5 FC group, 4.434 ± 4.790 in YCD K5 6 2B + saline group, K5 6 2B +5 FC group 2 2 .70 1 ± 2 35 0, K5 6 2B + saline group 2 4.46 0 ± 1.6 70; The difference between YCD K5 6 2B +5 FC group and YCD K5 6 2B + saline group was significant (P = 0 0 0 0 1), K5 6 2B +5 FC group and K5 6 2B + saline group, the difference was not statistically significant (P = 0. 0 96), indicating that 5 FC to YCD gene K5 6 2B leukemia cells have a significant killing effect, but had no effect on the growth of non-transgenic cells; YCD K5 6 2B +5 FC group on the tumor cells inoculated 12 to 15 days (5 FC treatment of 3 to 6 days) (the minimum relative volume was 0. 6 81). Pathological examination showed that 5 FC-treated tumors had arteriolar-centered necrosis. Conclusion The YCD 5 FC system transforms YCD in vivo
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