Tumor suppressor XAF1 induces apoptosis, inhibits angiogenesis and inhibits tumor growth in hepatocellular carcinoma.
Tumor suppressor XAF1 induces apoptosis, inhibits angiogenesis and inhibits tumor growth in hepatocellular carcinoma.
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肿瘤抑制因子 XAF1 诱导细胞凋亡、抑制血管生成并抑制肝细胞癌中的肿瘤生长。
DOI：
10.18632/oncotarget.2114
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发表时间：
2014-07-30
期刊：
影响因子：
--
通讯作者：
Tu SP
中科院分区：
文献类型：
--
作者：
Zhu LM;Shi DM;Dai Q;Cheng XJ;Yao WY;Sun PH;Ding Y;Qiao MM;Wu YL;Jiang SH;Tu SP
X-linked inhibitor of apoptosis (XIAP)-associated factor 1 （XAF1）是一种XIAP结合蛋白，是一种肿瘤抑制基因。XAF1在大多数人类恶性肿瘤中沉默或低表达。然而，XAF1在肝细胞癌（HCC）中的作用尚不清楚。在本研究中，我们研究了XAF1对肝癌细胞肿瘤生长和血管生成的影响。我们的研究结果显示，XAF1在HCC细胞系SMMC-7721、Hep G2和BEL-7404以及肝癌组织中的表达低于配对的非癌肝组织。腺病毒介导的XAF1表达（Ad5/F35-XAF1）显著抑制肝癌细胞增殖，诱导细胞凋亡，并呈剂量和时间依赖性。感染Ad5/F35-XAF1可诱导肝癌细胞中caspase -3、-8、-9和PARP的裂解。此外，Ad5/F35-XAF1治疗显著抑制肝癌细胞异种移植模型中的肿瘤生长。Western Blot和免疫组化染色显示，Ad5/F35-XAF1处理可抑制癌细胞和异种移植肿瘤组织中与肿瘤血管生成相关的血管内皮生长因子（VEGF）的表达。此外，Ad5/F35-XAF1处理可延长荷瘤小鼠的生存期。我们的研究结果表明，XAF1通过诱导细胞凋亡和抑制肿瘤血管生成来抑制肿瘤生长。XAF1可能是肝癌治疗的一个有希望的靶点。
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.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
9.7
作者：
Kempkensteffen, Carsten;Hinz, Stefan;Weikert, Steffen
通讯作者：
Weikert, Steffen
DOI：
10.1385/ijgc:33:1:79
发表时间：
2003-01-01
期刊：
International journal of gastrointestinal cancer
影响因子：
--
作者：
Fisher, William E;Berger, David H
通讯作者：
Berger, David H
影响因子：
6.4
作者：
Fang, XL;Liu, ZX;Xu, DW
通讯作者：
Xu, DW
影响因子：
8.8
作者：
Ngan, C. Y.;Yamamoto, H.;Seshimo, I.;Tsujino, T.;Man-i, M.;Ikeda, J-I;Konishi, K.;Takemasa, I.;Ikeda, M.;Sekimoto, M.;Matsuura, N.;Monden, M.
通讯作者：
Monden, M.