In vitro and in vivo suppression of hepatocellular carcinoma growth by midkine-antisense oligonucleotide-loaded nanoparticles.
OBJECTIVE
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.


CONCLUSIONS
NANO-ASODNs can significantly suppress the growth of HCC in vitro and in vivo.
Dai
Li-Cheng
LC
Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou, Zhejiang Province, China. dlc@hzhospital.com
Yao
Xing
X
Wang
Xiang
X
Niu
Shu-Qiong
SQ
Zhou
Lin-Fu
LF
Fu
Fang-Fang
FF
Yang
Shui-Xin
SX
Ping
Jin-Liang
JL
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000078792:Midkine; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000627:therapeutic use*; D011897:Random Allocation; D000509:alpha-Fetoproteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D016207:Cytokines; D016376:Oligonucleotides, Antisense; D000509:alpha-Fetoproteins; D000078792:Midkine