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 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.
Kawata
Eri
E
Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Japan.
Ashihara
Eishi
E
Kimura
Shinya
S
Takenaka
Kazumasa
K
Sato
Kiyoshi
K
Tanaka
Ruriko
R
Yokota
Asumi
A
Kamitsuji
Yuri
Y
Takeuchi
Miki
M
Kuroda
Junya
J
Tanaka
Fumihiro
F
Yoshikawa
Toshikazu
T
Maekawa
Taira
T
D000368:Aged; D000818:Animals; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1; C059821:atelocollagen