Administration of PLK-1 small interfering RNA with atelocollagen prevents the growth of liver metastases of lung cancer

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...

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Veröffentlicht in:Molecular cancer therapeutics 2008-09, Vol.7 (9), p.2904-2912
Hauptverfasser: 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
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container_end_page 2912
container_issue 9
container_start_page 2904
container_title Molecular cancer therapeutics
container_volume 7
creator 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
description 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 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. [Mol Cancer Ther 2008;7(9):2904–12]
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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 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. 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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. 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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. [Mol Cancer Ther 2008;7(9):2904–12]</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>18790771</pmid><doi>10.1158/1535-7163.MCT-08-0473</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Aged
Animals
Cell Cycle Proteins - antagonists & inhibitors
Cell Cycle Proteins - metabolism
Cell Death - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Collagen - administration & dosage
Collagen - pharmacology
Female
Humans
liver metastasis
Liver Neoplasms - prevention & control
Liver Neoplasms - secondary
Lung Neoplasms - enzymology
Lung Neoplasms - pathology
Lung Neoplasms - ultrastructure
Male
Mice
Mice, Nude
Middle Aged
PLK-1
Polo-Like Kinase 1
Protein Serine-Threonine Kinases - antagonists & inhibitors
Protein Serine-Threonine Kinases - metabolism
Proto-Oncogene Proteins - antagonists & inhibitors
Proto-Oncogene Proteins - metabolism
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - pharmacology
siRNA
Xenograft Model Antitumor Assays
title Administration of PLK-1 small interfering RNA with atelocollagen prevents the growth of liver metastases of lung cancer
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