Adenovirus-delivered CIAPIN1 small interfering RNA inhibits HCC growth in vitro and in vivo.
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 approximately 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.
Li
Xiaohua
X
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.
Pan
Yanglin
Y
Fan
Rui
R
Jin
Haifeng
H
Han
Shuang
S
Liu
Jie
J
Wu
Kaichun
K
Fan
Daiming
D
D000256:Adenoviridae; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle; D002455:Cell Division; D002470:Cell Survival; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics*; D008099:Liver / Q000502:physiology*; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C489114:CIAPIN1 protein, human; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering