Silencing of plasminogen activator inhibitor-1 suppresses colorectal cancer progression and liver metastasis.
BACKGROUND
Plasminogen activator inhibitor-1 (PAI-1) is reported to be expressed in many cancer cell types and regarded as one of the most informative biochemical markers for poor prognosis. However, no previous study has evaluated whether PAI-1 could serve as a target in antitumor and antimetastasis therapies of colorectal cancer (CRC).


METHODS
The plasma level of PAI-1 in CRC patients was detected and its correlation with the clinicopathologic features was evaluated. PAI-1 protein expression was assessed by Western blot assay and immunohistochemistry. The biologic consequences of PAI-1 silencing in colon cancer cell lines and CRC bearing nude mice were also investigated.


RESULTS
Plasma PAI-1 level was higher in CRC patients with liver metastasis and correlated with liver metastasis, tumor size, differentiation, serosa infiltration, Duke's stage, and lymphatic metastasis. PAI-1 protein expression in the CRC tissue of patients with liver metastasis was significantly greater than that in those without liver metastasis. In addition, the abilities of proliferation, invasion, and migration of CRC cells transfected with lentivirus expressing PAI-1 small interfering RNA were reduced significantly. Nude mice inoculated with PAI-1 knockdown cells also had fewer metastatic nodules in the liver and smaller tumor volumes.


CONCLUSIONS
Plasma PAI-1 level was increased in CRC patients with liver metastasis, and PAI-1 silencing may significantly compromise the malignant behaviors of CRC cells in vitro and in vivo. These findings may provide evidence for PAI-1 targeted therapy of CRC.
Department of General Surgery, Chinese People's Liberation Army No. 411 Hospital, Shanghai, China.
Han
H
Chen
Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Huan
H
Peng
Department of Diving Medicine, Second Military Medical University, Shanghai, China.
Wenwu
W
Liu
Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Yanping
Y
Sun
Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Ning
N
Su
Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Wentao
W
Tang
Department of Pathology, Chinese People's Liberation Army No. 411 Hospital, Shanghai, China.
Xiaoli
X
Zhang
Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Jian
J
Wang
Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Long
L
Cui
Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Pingfang
P
Hu
Department of General Surgery, Chinese People's Liberation Army No. 411 Hospital, Shanghai, China. Electronic address: liusheng196511@163.com.
Sheng
S
Liu
D000368:Aged; D000818:Animals; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D066298:In Vitro Techniques; D015994:Incidence; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000556:secondary*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology
D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D034741:RNA, Small Interfering; D020780:Matrix Metalloproteinase 9