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

Eri Kawata,Yuri Kamitsuji,Toshikazu Yoshikawa,Eishi Ashihara,Miki Takeuchi,Shinya Kimura,Ruriko Tanaka,Junya Kuroda,Kazumasa Takenaka,Kiyoshi Sato,Taira Maekawa,Fumihiro Tanaka,Asumi Yokota

doi:10.1158/1535-7163.mct-08-0473

Abstract

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.

Highlights

The discovery of RNA interference [1] led to its wide application as a powerful tool in postgenomic research
We recently showed that Polo-like kinases (PLK)-1 is a prognostic marker of urinary bladder carcinoma and that the intravesical administration of PLK-1 small interfering RNA (siRNA) inhibited the growth of bladder cancer in an orthotopic murine model [15]
We showed that PLK-1 is overexpressed in lung cancer tissues

Summary

Introduction

The discovery of RNA interference [1] led to its wide application as a powerful tool in postgenomic research. Small interfering RNA (siRNA), which induces RNA interference, has been experimentally introduced into cancer therapy. The establishment of siRNA therapy depends on the development of suitable delivery systems. Several useful drug delivery systems (DDS) for siRNA have been developed (2 – 6). Atelocollagen is one of the most unique and attractive DDS. It was developed as a biomaterial carrier for gene delivery and is obtained from type I collagen of calf dermis using pepsin treatment [3, 7]

Methods

Results

Conclusion