Department of General Surgery, Xinhua Hospital, Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Cancer Sci. 2012 Apr;103(4):723-30. doi: 10.1111/j.1349-7006.2012.02218.x. Epub 2012 Mar 4.
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.
组织因子途径抑制物-2（TFPI-2）已被确定为多种类型癌症的肿瘤抑制基因，但它在胆囊癌（GBC）中的作用尚未确定。本研究检测了 GBC 组织中的 TFPI-2 表达，并构建了腺病毒介导的 TFPI-2（Ad5-TFPI-2）基因转移，以恢复 GBC 细胞系（GBC-SD、SGC-996、NOZ）和异种移植肿瘤中 TFPI-2 的表达，评估了其对 GBC 生长的抑制活性。免疫组织化学染色显示 TFPI-2 在 GBC 组织标本中明显下调。Ad5-TFPI-2 可显著抑制 GBC 的体外和体内生长。凋亡分析和 Western blot 检测表明，Ad5-TFPI-2 通过促进细胞色素 c、Bax、caspase-3 和 -9 的活性和抑制 Bcl-2 的活性，诱导 GBC 细胞系和组织的凋亡。这些数据表明，TFPI-2 在 GBC 中作为肿瘤抑制因子发挥作用，并且可能在 GBC 的基因治疗中具有潜在作用。
