Administration of PLK-1 small interfering RNA with atelocollagen prevents the growth of liver metastases of lung cancer
Administration of PLK-1 small interfering RNA with atelocollagen prevents the growth of liver metastases of lung cancer
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DOI：
10.1158/1535-7163.mct-08-0473
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发表时间：
2008-09-01
影响因子：
5.7
通讯作者：
Maekawa, Taira
中科院分区：
文献类型：
--
作者：
Kawata, Eri;Ashihara, Eishi;Maekawa, Taira
肝转移是肺癌患者最重要的预后因素之一。然而，目前的疗法还不够。 RNA干扰为我们提供了治疗包括癌症在内的人类疾病的强大且有前景的方法。在此，我们研究了 PLK-1 小干扰 RNA (siRNA) 对人肺癌细胞系的体外影响，以及在小鼠肺癌肝转移模型中使用 PLK-1 siRNA 与去端肽胶原作为药物递送系统的体内用途。 PLK-1 在肺癌患者的细胞系和癌组织中过度表达。 PLK-1 siRNA 处理以浓度依赖性方式抑制生长并诱导细胞凋亡。为了验证体内功效，我们通过检测 Lv.1 后生物发光的减少，证实去端肽胶原在植入荧光素酶标记的 A549（LUC）细胞模型中是一种有用的药物递送系统。注射荧光素酶 GL3 siRNA/去端肽胶原。 PLK-1 siRNA/去端肽胶原也成功转染到细胞中并抑制转移的进展。这项研究显示了静脉注射的功效。 PLK-1 siRNA/去端肽胶原蛋白治疗肺癌肝转移。我们相信 siRNA 疗法将成为治疗晚期肺癌的一种强大且有前景的策略。
Liver metastasis is one of the most important prognostic factors in lung cancer patients. However, current therapies are not sufficient. RNA interference provides us a powerful and promising approach for treating human diseases including cancers. Herein, we investigated the in vitro effects of PLK-1 small interfering RNA (siRNA) on human lung cancer cell lines and the in vivo usage of PLK-1 siRNA with atelocollagen as a drug delivery system in a murine liver metastasis model of lung cancer. PLK-1 was overexpressed in cell lines and in cancerous tissues from lung cancer patients. PLK-1 siRNA treatment inhibited growth and induced apoptosis in a concentration-dependent manner. To verify in vivo efficacy, we confirmed that atelocollagen was a useful drug delivery system in our model of implanted luciferase-labeled A549(LUC) cells by detecting reduced bioluminescence after an Lv. injection of luciferase GL3 siRNA/atelocollagen. PLK-1 siRNA/atelocollagen was also successfully transfected into cells and inhibited the progression of metastases. This study shows the efficacy of i.v. administration of PLK-1 siRNA/atelocollagen for liver metastases of lung cancer. We believe siRNA therapy will be a powerful and promising strategy against advanced lung cancer.