Journal
MOLECULAR CANCER THERAPEUTICS
Volume 7, Issue 9, Pages 2904-2912Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-08-0473
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Funding
- Research for Promoting Technological Seeds
- Japan Science and Technology Agency
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Yasuda Medical Research Foundation
- Japan Leukemia Research Fund
- Uehara Memorial Foundation
- Japan Medical Association
- Sagawa Foundation for Cancer Research
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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.
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