Kawata Eri, Ashihara Eishi, Kimura Shinya, Takenaka Kazumasa, Sato Kiyoshi, Tanaka Ruriko, Yokota Asumi, Kamitsuji Yuri, Takeuchi Miki, Kuroda Junya, Tanaka Fumihiro, Yoshikawa Toshikazu, Maekawa Taira
Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Japan.
Mol Cancer Ther. 2008 Sep;7(9):2904-12. doi: 10.1158/1535-7163.MCT-08-0473.
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 A549LUC cells by detecting reduced bioluminescence after an i.v. 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.
肝转移是肺癌患者最重要的预后因素之一。然而，目前的治疗方法并不充分。RNA干扰为我们提供了一种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作用，以及在肺癌小鼠肝转移模型中以去端肽胶原蛋白作为药物递送系统的PLK-1 siRNA的体内应用。PLK-1在肺癌患者的细胞系和癌组织中过表达。PLK-1 siRNA处理以浓度依赖性方式抑制生长并诱导凋亡。为了验证体内疗效，我们通过检测静脉注射荧光素酶GL3 siRNA/去端肽胶原蛋白后生物发光的降低，证实去端肽胶原蛋白在我们植入荧光素酶标记的A549LUC细胞的模型中是一种有用的药物递送系统。PLK-1 siRNA/去端肽胶原蛋白也成功转染到细胞中并抑制转移进展。本研究显示了静脉注射PLK-1 siRNA/去端肽胶原蛋白对肺癌肝转移的疗效。我们相信siRNA疗法将成为对抗晚期肺癌的一种强大且有前景的策略。
