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Carcinogenesis Advance Access originally published online on February 24, 2008
Carcinogenesis 2008 29(8):1587-1593; doi:10.1093/carcin/bgn052
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
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Adenovirus-delivered CIAPIN1 small interfering RNA inhibits HCC growth in vitro and in vivo

Xiaohua Li, Yanglin Pan, Rui Fan, Haifeng Jin, Shuang Han, Jie Liu, Kaichun Wu and Daiming Fan*

State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, 17 Changlexilu, Shaanxi Province, Xi'an 710032, People's Republic of China

* To whom correspondence should be addressed. Tel: +86 29 84773974; Fax: +86 29 82539041; E-mail: fandaimingfdm{at}yahoo.com.cn

Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. The specific cellular gene alterations responsible for hepatocarcinogenesis are not well known. Cytokine-induced antiapoptotic molecule (CIAPIN1), a recently reported antiapoptotic molecule which plays an essential role in mouse definitive hematopoiesis, is considered a downstream effecter of the receptor tyrosine kinase–Ras signaling pathway. However, the exact function of this gene in tumors is not clear. In this study, we reported that CIAPIN1 is highly expressed in HCC as compared with non-tumor hepatic tissue (P < 0.05). We employed adenovirus-mediated RNA interference technique to knock down CIAPIN1 expression in HCC cells and observed its effects on HCC cell growth in vitro and in vivo. Among the four HCC and one normal human liver cell lines we analyzed, CIAPIN1 was highly expressed in HCC cells. Knock down of CIAPIN1 could inhibit HCC cell proliferation by inhibiting the cell cycle S-phase entry. Soft agar colony formation assay indicated that the colony-forming ability of SMMC-7721 cells decreased by ~70% after adenovirus AdH1-small interfering RNA (siRNA)/CIAPIN1 infection. In vivo experiments showed that adenovirus AdH1-siRNA/CIAPIN1 inhibited the tumorigenicity of SMMC-7721 cells and significantly suppressed tumor growth when injected directly into tumors. These results suggest that knock down of CIAPIN1 by adenovirus-delivered siRNA may be a potential therapeutic strategy for treatment of HCC in which CIAPIN1 is overexpressed.

Abbreviations: FL, fetal liver; GFP, green fluorescent protein; HCC, hepatocellular carcinoma; mRNA, messenger RNA; MOI, multiplicity of infection; PCR, polymerase chain reaction; PBS, phosphate-buffered saline; RNAi, RNA interference; siRNA, small interfering RNA

Received January 11, 2007; revised February 11, 2008; accepted February 12, 2008.


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