title: Tumor suppressor XAF1 induces apoptosis, inhibits angiogenesis and inhibits tumor growth in hepatocellular carcinoma.
abstract: X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1), a XIAP-binding protein, is a tumor suppressor gene. XAF1 was silent or expressed lowly in most human malignant tumors. However, the role of XAF1 in hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the effect of XAF1 on tumor growth and angiogenesis in hepatocellular cancer cells. Our results showed that XAF1 expression was lower in HCC cell lines SMMC-7721, Hep G2 and BEL-7404 and liver cancer tissues than that in paired non-cancer liver tissues. Adenovirus-mediated XAF1 expression (Ad5/F35-XAF1) significantly inhibited cell proliferation and induced apoptosis in HCC cells in dose- and time- dependent manners. Infection of Ad5/F35-XAF1 induced cleavage of caspase -3, -8, -9 and PARP in HCC cells. Furthermore, Ad5/F35-XAF1 treatment significantly suppressed tumor growth in a xenograft model of liver cancer cells. Western Blot and immunohistochemistry staining showed that Ad5/F35-XAF1 treatment suppressed expression of vascular endothelial growth factor (VEGF), which is associated with tumor angiogenesis, in cancer cells and xenograft tumor tissues. Moreover, Ad5/F35-XAF1 treatment prolonged the survival of tumor-bearing mice. Our results demonstrate that XAF1 inhibits tumor growth by inducing apoptosis and inhibiting tumor angiogenesis. XAF1 may be a promising target for liver cancer treatment.
authors: Department of Gastroenterology, No.3 People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Li Ming
authors: LM
authors: Zhu
authors: Department of Gastroenterology, Huadong Hospital, Shanghai Fudang University, Shanghai, China.
authors: Dong Mei
authors: DM
authors: Shi
authors: Department of Gastroenterology, No.3 People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Qiang
authors: Q
authors: Dai
authors: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Xiao Jiao
authors: XJ
authors: Cheng
authors: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Wei Yan
authors: WY
authors: Yao
authors: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Ping Hu
authors: PH
authors: Sun
authors: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Yanfei
authors: Y
authors: Ding
authors: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Min Min
authors: MM
authors: Qiao
authors: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Yun Lin
authors: YL
authors: Wu
authors: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Shi Hu
authors: SH
authors: Jiang
authors: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Shui Ping
authors: SP
authors: Tu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D015316:Genetic Therapy; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008113:Liver Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C417551:XAF1 protein, human