Adenovirus-mediated gene transfer of tissue factor pathway inhibitor-2 inhibits gallbladder carcinoma growth in vitro and in vivo.
Tissue factor pathway inhibitor-2 (TFPI-2) has been identified as a tumor suppressor gene in several types of cancers, but its role in gallbladder carcinoma (GBC) is yet to be determined. In the present study, TFPI-2 expression in GBC tissues was examined, and its inhibitory activities against GBC growth were evaluated in vitro and in vivo after adenovirus-mediated gene transfer of TFPI-2 (Ad5-TFPI-2) was constructed to restore the expression of TFPI-2 in GBC cell lines (GBC-SD, SGC-996, NOZ) and xenograft tumors. Immunohistochemical staining showed that TFPI-2 was significantly downregulated in GBC tissue specimens. Ad5-TFPI-2 could significantly inhibit GBC growth both in vitro and in vivo. Apoptosis analysis and western blotting assay demonstrated that Ad5-TFPI-2 could induce the apoptosis of both GBC cell lines and tissues by promoting the activities of cytochrome c, Bax, caspase-3 and -9 and suppressing Bcl-2 activity. These data indicated that TFPI-2 acts as a tumor suppressor in GBC, and may have a potential role in gene therapy for GBC.
Department of General Surgery, Xinhua Hospital, Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Yiyu
Y
Qin
Shenglai
S
Zhang
Wei
W
Gong
Jiyu
J
Li
Jianguang
J
Jia
Zhiwei
Z
Quan
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D016153:Genes, Suppressor; D005822:Genetic Vectors; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D029122:Murine pneumonia virus; D009368:Neoplasm Transplantation
D006023:Glycoproteins; C021240:tissue-factor-pathway inhibitor 2