Anti-tumor efficacy of naked siRNAs for ERBB3 or AKT2 against lung adenocarcinoma cell xenografts.
Anti-tumor efficacy of naked siRNAs for ERBB3 or AKT2 against lung adenocarcinoma cell xenografts.
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DOI：
10.1002/ijc.26041
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发表时间：
2012-01-15
影响因子：
6.4
通讯作者：
Anderson, Lucy M.
中科院分区：
文献类型：
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作者：
Sithanandam, Gunamani;Fornwald, Laura W.;Fields, Janet R.;Morris, Nicole L.;Anderson, Lucy M.
使用sirna对抗特定的分子靶标具有癌症治疗的潜力，但一直被认为是受限于需要配方来改善细胞摄取。肺腺癌细胞在培养过程中被ERBB3受体或其下游信号伙伴AKT2的sirna显著抑制。我们现在证明，在4个不同的实验中，ERBB3或AKT2的裸的、未配制的sirna以生理盐水的形式静脉注射，每周5次，每次2 μg/g，持续3周（总剂量30 μg/g），可以有效抑制A549人肺腺癌细胞异种移植物在胸腺小鼠中的生长，每组12只小鼠。与盐水处理或未处理的对照组相比，ERBB3和AKT2 sirna平均抑制生长70-90%；非沉默siRNA无显著影响。总剂量为12 μg/g时，效果较小但显著。使用较高剂量，效果在治疗结束后持续数周。ERBB3和AKT2 mrna和蛋白出现预期的减少，并与肿瘤体积减小相关。血清细胞因子无明显变化。这些结果表明，ERBB3或AKT2的裸sirna可能具有治疗肺癌的潜力。
The use of siRNAs against specific molecular targets has potential for cancer therapy, but has been thought to be limited by the need for formulation to improve cellular uptake. Lung adenocarcinoma cells are markedly suppressed in culture by siRNAs to the receptor ERBB3 or its downstream signaling partner AKT2. We now demonstrate that naked, unformulated siRNAs to ERBB3 or AKT2, administered i.v. as saline solutions, 2 μg/g 5 times per week for 3 weeks (total dose 30 μg/g), were effective suppressors of growth of A549 human lung adenocarcinoma cell xenografts in athymic mice, 12 mice per group, in 4 different experiments. ERBB3 and AKT2 siRNAs each inhibited growth by 70–90% on average, compared with saline-treated or untreated controls; a non-silencing siRNA was without significant effect. Lesser but significant effects were noted with a total dose of 12 μg/g. With the higher dose, effects persisted for several weeks after the end of treatment. Expected reductions of ERBB3 and AKT2 mRNAs and proteins occurred, and correlated with decrease in tumor volume. There were no significant changes in serum cytokines. These results show that naked siRNAs to ERBB3 or AKT2 may have potential for lung cancer therapy.
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DOI：
10.1158/1078-0432.ccr-08-2921
发表时间：
2009-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Sun M;Behrens C;Feng L;Ozburn N;Tang X;Yin G;Komaki R;Varella-Garcia M;Hong WK;Aldape KD;Wistuba II
通讯作者：
Wistuba II
影响因子：
64.8
作者：
Castanotto, Daniela;Rossi, John J.
通讯作者：
Rossi, John J.
影响因子：
5.7
作者：
Sakai, Kazuko;Yokote, Hideyuki;Nishio, Kazuto
通讯作者：
Nishio, Kazuto
影响因子：
7.3
作者：
Amin DN;Campbell MR;Moasser MM
通讯作者：
Moasser MM
DOI：
10.1073/pnas.0912101106
发表时间：
2009-12-22
影响因子：
11.1
作者：
Jura, Natalia;Shan, Yibing;Kuriyan, John
通讯作者：
Kuriyan, John