Suppression of adenine nucleotide translocase-2 by vector-based siRNA in human breast cancer cells induces apoptosis and inhibits tumor growth in vitro and in vivo.
Suppression of adenine nucleotide translocase-2 by vector-based siRNA in human breast cancer cells induces apoptosis and inhibits tumor growth in vitro and in vivo.
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DOI：
10.1186/bcr1857
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Kim CW
中科院分区：
文献类型：
--
作者：
Jang JY;Choi Y;Jeon YK;Kim CW
腺嘌呤核苷酸转运子（ANT）2在增殖细胞中高度表达，并且已知癌细胞中的ANT 2诱导与糖酵解代谢和致癌作用直接相关。此外，ANT 2抑制导致人类细胞的生长停滞，这意味着ANT 2是基于分子靶向的癌症治疗的候选者。我们利用ANT 2特异性RNA干扰的方法来抑制ANT 2的表达，以评估其在体外和体内的抗肿瘤作用。具体而言，为了研究ANT 2抑制的治疗潜力，我们使用了基于DNA载体的RNA干扰方法，通过表达shRNA来敲低过表达ANT 2的乳腺癌细胞系中的ANT 2。乳腺癌细胞系MDA-MB-231中的ANT 2 shRNA处理抑制细胞生长以及增殖。此外，从ANT 2 shRNA处理的乳腺癌细胞中观察到细胞周期停滞、ATP耗竭和以线粒体膜的潜在破坏为特征的凋亡性细胞死亡。用ANT 2 shRNA转染的凋亡乳腺癌细胞也诱导了细胞毒性旁观者效应，该效应对邻近细胞产生坏死细胞死亡。ANT 2shRNA转染细胞内TNFα和TNF受体I水平升高，旁观者效应可被抗TNF α抗体部分阻断。最终，ANT 2 shRNA有效地抑制了体内肿瘤生长。这些结果表明，基于载体的ANT 2 RNA干扰可能是一种有效的分子治疗方法与ANT 2高表达的乳腺癌。
Adenine nucleotide translocator (ANT) 2 is highly expressed in proliferative cells, and ANT2 induction in cancer cells is known to be directly associated with glycolytic metabolisms and carcinogenesis. In addition, ANT2 repression results in the growth arrest of human cells, implying that ANT2 is a candidate for cancer therapy based on molecular targeting. We utilized an ANT2-specific RNA interference approach to inhibit ANT2 expression for evaluating its antitumor effect in vitro and in vivo. Specifically, to investigate the therapeutic potential of ANT2 repression, we used a DNA vector-based RNA interference approach by expressing shRNA to knockdown ANT2 in breast cancer cell lines overexpressing ANT2. ANT2 shRNA treatment in breast cancer cell line MDA-MB-231 repressed cell growth as well as proliferation. In addition, cell cycle arrest, ATP depletion and apoptotic cell death characterized by the potential disruption of mitochondrial membrane were observed from the ANT2 shRNA-treated breast cancer cells. Apoptotic breast cancer cells transfected with ANT2 shRNA also induced a cytotoxic bystander effect that generates necrotic cell death to the neighboring cells. The intracellular levels of TNFα and TNF-receptor I were increased in ANT2 shRNA transfected cells and the bystander effect was partly blocked by anti-TNFα antibody. Ultimately, ANT2 shRNA effectively inhibited tumor growth in vivo. These results suggest that vector-based ANT2 RNA interference could be an efficient molecular therapeutic method for breast cancer with high expression of ANT2.
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腺嘌呤核苷酸易位酶-1是渗透性过渡孔的成分，可以主要诱导凋亡。
影响因子：
7.8
作者：
Bauer, M K;Schubert, A;Rocks, O;Grimm, S
通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
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DOI：
10.1385/1-59259-750-5:255
发表时间：
2004-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Hannon, Gregory J;Conklin, Douglas S
通讯作者：
Conklin, Douglas S
DOI：
10.1073/pnas.1031523100
发表时间：
2003-05-13
影响因子：
11.1
作者：
Liu, XQ;Erikson, RL
通讯作者：
Erikson, RL
DOI：
10.1073/pnas.132269599
发表时间：
2002-06-25
影响因子：
11.1
作者：
Liu, XQ;Erikson, RL
通讯作者：
Erikson, RL