氧化铁磁性纳米颗粒介导wt-p53基因对肺腺癌细胞增殖和凋亡的影响

Influence of magnetic iron oxide nanoparticle-mediated wild-type p53 gene on proliferation and apoptosis of human lung adeno-carcinoma cells

目的:探讨氧化铁磁性纳米颗粒介导野生型p53基因(wild type p53,wt-p53)对耐顺铂人肺腺癌细胞A549/DDP增殖抑制和凋亡诱导的作用。方法:氧化铁磁性纳米颗粒介导wt-p53转染肺腺癌细胞A549/DDP作为实验组,以纳米颗粒介导空载体pcDNA3转染作为阴性对照组,脂质体介导wt-p53转染作阳性对照组。MTT法和绘制生长曲线观察基因转染对A549/DDP细胞增殖抑制作用,荧光显微镜、流式细胞术观察其对A549/DDP细胞诱导凋亡作用,RT-PCR检测其对A549/DDP细胞Bax mRNA表达的影响。结果:氧化铁磁性纳米颗粒介导wt-p53对人肺腺癌细胞A549/DDP增殖有持续的抑制作用,而以脂质体介导wt-p53对增殖抑制作用持续时间短暂;纳米颗粒介导wt-p53对人肺腺癌细胞A549/DDP诱导凋亡作用明显强于以脂质体载体;同时介导wt-p53上调Bax mRNA表达水平的作用也明显强于以脂质体载体。结论:氧化铁磁性纳米颗粒介导wt-p53转染对人肺腺癌细胞A549/DDP有持续的增殖抑制和诱导凋亡的作用。

Objective： To study roles of magnetic iron oxide nanoparticle-mediated wild-type p53 gene delivery in inhibiting proliferation and inducing apoptosis of human lung adeno-careinoma cell line A549/CDDP. Methods： The magnetic iron oxide nanoparticles-mediated wild-type p53 gene delivery was used in treatment groups; nanoparticle-mediated peDNA3 vector was used as negative control; and liposome mediated wt-p53 gene was used as positive control. The proliferation inhibition of A549/DDP cells was investigated by MTT assay in the 3 groups and the growth curves were drawn. The apoptosis of cells were detected by flow cytometory and fluorescent microscope. RT-PCR was employed to examine the variation of Bax mRNA expression. Results： Wt-p53 DNA-loaded magnetic iron oxide nanoparticles demonstrated a sustained and significantly greater antiproliferative effect than those lipofectamine-mediated wt-p53 DNA. Wt-p53 DNA-loaded magnetic iron oxide nanoparticles also induced stronger apoptosis of A549/DDP cells than lipofectamine-mediated wt-p53 DNA. Expression of Bax mRNA in A549/CDDP cells in magnetic iron oxide nanoparticle group was obviously higher than lipofeetaine-mediated group. Conclusion： Magnetic iron oxide nanoparticle-mediated wild-type p53 gene delivery has sustained antiproliferative and apoptosis-inducing effects on human lung adeno-carcinoma cell line A549/CDDP.