Original Articles
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Apr 28, 2009; 15(16): 1966-1972
Published online Apr 28, 2009. doi: 10.3748/wjg.15.1966
In vitro and in vivo suppression of hepatocellular carcinoma growth by midkine-antisense oligonucleotide-loaded nanoparticles
Li-Cheng Dai, Xing Yao, Xiang Wang, Shu-Qiong Niu, Lin-Fu Zhou, Fang-Fang Fu, Shui-Xin Yang, Jin-Liang Ping
Li-Cheng Dai, Xiang Wang, Shu-Qiong Niu, Shui-Xin Yang, Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
Xing Yao, Department of General Surgery, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
Lin-Fu Zhou, Fang-Fang Fu, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang Province, China
Jin-Liang Ping, Department of Pathology, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
Author contributions: Yao X, Niu SQ, Zhou LF and Wang X performed the majority of the experiments; Ping JL, Fu FF and Yang SX provided vital reagents and analytical tools; Dai LC designed the study and wrote the manuscript.
Correspondence to: Li-Cheng Dai, Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China. dlc@hzhospital.com
Telephone: +86-572-2033020
Fax: +86-572-2033020
Received: December 12, 2008
Revised: January 19, 2009
Accepted: January 26, 2009
Published online: April 28, 2009
Abstract

AIM: To synthesize antisense oligonucleotides (ASODNs) of midkine (MK), package the ASODNs with nanoparticles, and to inhibit hepatocellular carcinoma (HCC) growth using these nanoparticles.

METHODS: HepG2 cell proliferation was analyzed in vitro using the 3-(4,5-dimethythiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, inner salt assay. The in vivo activity of nanoparticles delivering the MK-ASODNs was analyzed by histopathological and immunohistochemical staining and quantitative real time polymerase chain reaction (PCR).

RESULTS: The in vitro proliferation of HepG2 cells was significantly inhibited by the nanoparticles packaged with MK-ASODNs (NANO-ASODNs). Furthermore, the NANO-ASODNs significantly inhibited the growth of HCC in the mouse model.

CONCLUSION: NANO-ASODNs can significantly suppress the growth of HCC in vitro and in vivo.

Keywords: Midkine, Nanoparticles, Hepatocellular carcinoma, Inhibition, Drug delivery