[Inhibitory effects of transfection of arresten gene on liver metastasis from colorectal cancer in nude mice].
OBJECTIVE
Liver metastasis is the most common cause of death due to colorectal cancer. Above 50% colorecal cancer patients have liver metastasis. This study was to investigate the effect of transfection of arresten gene on liver metastasis from human colorectal cancer (LoVo) xenografts in nude mice.


METHODS
The eukaryotic expression plasmid pSecTag2-arresten was transfected into human colorectal cancer cell line LoVo using Lipofectamine 2000. Cells were divided into pSecTag2-arresten group, pSecTag2 group and control group. Expressions of arresten at mRNA and protein levels were detected by RT-PCR and Western blot, respectively. The effect of arresten on proliferation of LoVo cells was measured using MTT assay. LoVo cells transfected with pSecTag2-arresten were implanted into nude mice to investigate the effect of arresten on hepatic metastasis of colorectal cancer. Microvessel density (MVD) of xenograft tumors was assessed using immunohistochemistry with FVIIIRag monoclonal antibody.


RESULTS
Arresten was successfully transfected and expressed in LoVo cells. Inhibition of cell proliferation did not differ significantly in all three groups (P > 0.05). The metastastic rate was lower in pSecTag2-arresten group [(25.1+/-2.1)%] than in pSecTag2 group [(87.1+/-1.2)% or control group [(87.1+/-1.5)%] in LoVo cells (P < 0.05). The number of xenograft tumors and MVD were higher in pSecTag2-arresten group [(4.5 +/-0.5) and (15.3+/-3.5)] than in pSecTag2 group [(19.6+/-2.5) and (42.2+/-2.6)] or in control group [(20.4+/-2.5)and (45.6+/-5.1)] in nude mice.


CONCLUSIONS
Arresten can inhibit hepatic metastasis from colorectal cancer, which may be through its inhibition on tumor angiogenesis.
Department of General Surgery, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510120, P.R.China.
Miao-Yun
MY
Long
Hong-Hao
HH
Li
Jun-Yao
JY
Xu
Dong-Min
DM
Lai
Zhen-Hong
ZH
Weng
D020533:Angiogenesis Inhibitors / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D024141:Collagen Type IV / Q000096:biosynthesis* / Q000235:genetics; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000473:pathology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
D020533:Angiogenesis Inhibitors; D024141:Collagen Type IV; D010446:Peptide Fragments; D012333:RNA, Messenger