Open AccessAdenovirus‐mediated gene transfer of tissue factor pathway inhibitor‐2 inhibits gallbladder carcinoma growth in vitro and in vivo
Author(s) -
Qin Yiyu,
Zhang Shenglai,
Gong Wei,
Li Jiyu,
Jia Jianguang,
Quan Zhiwei
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02218.x
Subject(s) - in vivo , cancer research , tissue factor pathway inhibitor , in vitro , biology , apoptosis , microbiology and biotechnology , immunohistochemistry , pathology , immunology , medicine , tissue factor , biochemistry , coagulation
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 ( A d5‐ 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. A d5‐ TFPI ‐2 could significantly inhibit GBC growth both in vitro and in vivo . Apoptosis analysis and western blotting assay demonstrated that A d5‐ TFPI ‐2 could induce the apoptosis of both GBC cell lines and tissues by promoting the activities of cytochrome c , B ax, caspase‐3 and ‐9 and suppressing B cl‐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 . ( Cancer Sci 2012; 103: 723–730)