Research Article

新型联合溶瘤腺病毒基因治疗武装Dm-dNK和CD40L治疗乳腺癌

卷 19, 期 1, 2019

页: [54 - 65] 页: 12

弟呕挨: 10.2174/1566523219666190307094713

价格: $65

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摘要

背景:通过条件复制的腺病毒,果蝇脱氧核糖核苷激酶(Dm-dNK)自杀基因治疗和外源性CD40配体(CD40L)-CD40相互作用可以选择性地杀死肿瘤而不损伤正常组织。 目的:为进一步提高癌症杀灭效果,我们研究了基于Dm-dNK自杀基因和外源性CD40L的选择性溶瘤腺病毒载体的体外和体内联合癌基因治疗对乳腺癌细胞的治疗效果。 方法:使用腺病毒载体P74产生一系列条件复制的腺病毒:P74-dNK,P74-CD40L(分别表达Dm-dNK或CD40L)和P74-dNK-CD40L(表达组合的Dm-dNK和CD40L)。用腺病毒处理乳腺癌细胞系(MDA-MB-231,MCF-7)和非肿瘤细胞系(MRC5),MTT法测定细胞毒性,72h后用流式细胞仪检测细胞凋亡。我们还使用具有MDA-MB-231细胞的小鼠异种移植模型评估了体内细胞杀伤效率。 结果与讨论:Dm-dNK和CD40L的共表达降低了MDAMB-231或MCF7癌细胞的细胞增殖,并诱导了TERT和CD40阳性癌细胞中更多的凋亡,但不是正常的MRC5细胞。与任何单一治疗相比,在联合治疗组中也观察到肿瘤体积的显着减少。 结论:我们的数据表明,使用含有Dm-dNK自杀基因和外源性CD40结扎(CD40L-CD40)的条件复制腺病毒的联合基因治疗可以增强选择性肿瘤细胞的杀伤作用。

关键词: 自杀遗传疗法,CD40配体,乳腺肿瘤,腺病毒科,OVs,PCR。

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