Carcinogenesis Advance Access published online on February 24, 2008
Carcinogenesis, doi:10.1093/carcin/bgn052
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Adenovirus-delivered CIAPIN1 small interfering RNA inhibits HCC growth in vitro and in vivo

State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, the Fourth Military Medical University, 17 Changlexilu, Xi'an, Shaanxi Province, 710032, P.R.China
To whom requests for reprints should be addressed, at State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, the Fourth Military Medical University, 17 Changlexilu, Xi'an, Shaanxi Province, 710032, P.R.China. 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. 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 hepatocellular carcinoma cells and observed its effects on hepatocellular carcinoma cell growth in vitro and in vivo. Among the four hepatocellular carcinoma and one normal human liver cell lines we analyzed, CIAPIN1 was highly expressed in hepatocellular carcinoma cells. Knockdown of CIAPIN1 could inhibit HCC cells proliferation by inhibiting the cell cycle S-phase entry. Soft agar colony formation assay indicated that the colony forming ability of SMMC7721 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 SMMC7721 cells and significantly suppressed tumor growth when injected directly into tumors. These results suggest that knockdown of CIAPIN1 by adenovirus-delivered siRNA may be a potential therapeutic strategy for treatment of hepatocellular carcinoma in which CIAPIN1 is overexpressed.
Key Words: CIAPIN1 adenovirus tumorigenesis gene therapy hepatocellular carcinoma
Received July 11, 2007; revised February 11, 2008; accepted February 12, 2008.