Remarkable induction of apoptosis in cancer cells by a novel cationic liposome complexed with a bcl-2 antisense oligonucleotide.
Remarkable induction of apoptosis in cancer cells by a novel cationic liposome complexed with a bcl-2 antisense oligonucleotide.
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DOI：
10.1016/s0168-3659(02)00484-4
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发表时间：
2003-03
期刊：
影响因子：
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通讯作者：
Shoichiro Noguchi;N. Hirashima;T. Furuno;M. Nakanishi
中科院分区：
文献类型：
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作者：
Shoichiro Noguchi;N. Hirashima;T. Furuno;M. Nakanishi
我们最近报道了一种用于脂质体介导的基因转染的具有羟乙基氨基头部基团的新型阳离子胆固醇衍生物，胆固醇基-3 β-羧酰胺基乙烯-N-羟乙胺（I）[FEBS Lett.，408（1997）232]。在本论文中，我们研究了这种新型的阳离子脂质体是否在本质上是突出的，以抑制人类癌细胞的细胞生长。将Bcl-2反义硫代磷酸寡核苷酸（AS-ODN）与含有衍生物（I）的阳离子脂质体复合，并将它们导入人宫颈上皮癌细胞系HeLa和小鼠成纤维细胞NIH 3 T3细胞中。靶向/bcl-2基因的AS-ODNs在HeLa和NIH 3 T3细胞中可能诱导凋亡（在某些情况下包括坏死），然而，对应于乱序序列控制的无义寡核苷酸（NS-ODNs）几乎不诱导凋亡。细胞凋亡的诱导作用远大于市售DC-Chol脂质体。FITC标记的bcl-2 AS-ODNs的荧光强度在细胞核中特异性地被发现。AS-ODNs的强度与通过Western印迹分析在靶细胞中观察到的Bcl-2蛋白的量基本一致。结果表明，这种新的阳离子胆固醇衍生物可能是非常有前途的脂质体介导的基因靶向在体外和体内。
We reported recently a novel cationic cholesterol derivative with a hydroxyethylamino head group, cholesteryl-3β-carboxyamidoethylene-N-hydroxyethylamine (I) for liposome-mediated gene transfection [FEBS Lett., 408 (1997) 232]. In the present paper we have studied whether this novel cationic liposome is prominent in nature to suppress cell growth of human cancer cells. Bcl-2 antisense phosphorothioate oligonucleotides (AS-ODNs) were complexed with the cationic liposomes with the derivative (I) and they were introduced into human cervix epithelial carcinoma cell lines HeLa, and mouse fibroblast NIH3T3 cells. An AS-ODNs targeting/bcl-2 gene induced probably apoptosis (including necrosis in some cases) in HeLa and NIH3T3 cells, however, nonsense oligonucleotides (NS-ODNs) corresponding to a scrambled-sequence control hardly induced apoptosis. Induction of apoptosis was much greater than that by commercially available DC-Chol liposomes. Fluorescence intensities of FITC-conjugated bcl-2 AS-ODNs were specifically found in the nucleus. The intensity of the AS-ODNs was mostly consistent with the amounts of Bcl-2 proteins observed by Western blot analysis in the target cells. The results showed the possibility that this new cationic cholesterol derivative might be very promising to be used for liposome-mediated gene targeting in vitro and in vivo.