利用蓬乱蛋白和顺铂靶向Wnt信号通路可协同抑制间皮瘤细胞生长。
Targeting the Wnt signaling pathway with dishevelled and cisplatin synergistically suppresses mesothelioma cell growth.
作者信息
Uematsu Kazutsugu, Seki Nobuhiko, Seto Takashi, Isoe Chie, Tsukamoto Hideo, Mikami Iwao, You Liang, He Biao, Xu Zhidong, Jablons David M, Eguchi Kenji
机构信息
Division of Clinical Oncology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
出版信息
Anticancer Res. 2007 Nov-Dec;27(6B):4239-42.
BACKGROUND
We have previously found that Wnt signaling is activated in mesothelioma cells. To clarify the effect of blocking Wnt signaling in mesothelioma, the expression of dishevelled (Dvl), an intermediator of Wnt signaling, was down-regulated by a reformed type of small interfering RNA (siRNA), stealth RNAi, which can reduce the cytotoxic interferon response unlike conventional siRNA.
MATERIALS AND METHODS
Mesothelioma cell lines were transfected with stealth RNAi of Dvl, and cell growth and colony formation were examined. The synergistic effect on cell growth of Dvl stealth RNAi and cisplatin in combination was evaluated.
RESULTS
Dvl stealth RNAi down-regulated the expression of Dvl-3 in mesothelioma cells and induced cell cycle aberration which caused suppression of cell growth. Colony formation was also suppressed. Dvl stealth RNAi and cisplatin in combination suppressed cell growth synergistically.
CONCLUSION
Our data suggest that inhibition of Wnt signaling leads to significant antitumor effects.
背景
我们之前发现Wnt信号通路在间皮瘤细胞中被激活。为阐明阻断Wnt信号通路对间皮瘤的影响，通过一种改良型小干扰RNA（siRNA），即隐形RNA干扰，下调Wnt信号通路的中介蛋白散乱蛋白（Dvl）的表达，与传统siRNA不同，隐形RNA干扰可降低细胞毒性干扰素反应。
材料与方法
用Dvl的隐形RNA干扰转染间皮瘤细胞系，检测细胞生长和集落形成情况。评估Dvl隐形RNA干扰与顺铂联合对细胞生长的协同作用。
结果
Dvl隐形RNA干扰下调间皮瘤细胞中Dvl-3的表达，并诱导细胞周期异常，从而抑制细胞生长。集落形成也受到抑制。Dvl隐形RNA干扰与顺铂联合可协同抑制细胞生长。
结论
我们的数据表明，抑制Wnt信号通路可产生显著的抗肿瘤作用。
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