Adenovirus-delivered CIAPIN1 small interfering RNA inhibits HCC growth in vitro and in vivo

Abstract

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.

TAT-LHRH conjugated low molecular weight chitosan as a gene carrier specific for hepatocellular carcinoma cells

“…3 Long-term survival of patients with HCC is uncommon due to the frequent presence of reoccurrence, metastasis, or the development of new primaries. 4 Curative treatment such as hepatic resection and liver transplantation can be utilized when HCC is diagnosed at an early stage. 5,6 Unfortunately, when diagnosed the vast majority of liver cancers are inoperable, [7][8][9] and thus the patients have to receive chemotherapy, which has limited success due to the fact that HCC is intrinsically resistant to standard chemotherapeutic agents.…”

CIAPIN1 confers multidrug resistance through up-regulation of MDR-1 and Bcl-L in LoVo/Adr cells and is independent of p53

“…In a previous study, li et al observed that, in p53 wild-type Hepg2 and sMMc-7721 cells, apoptosis induced by AdsicIApIn1 (adenovirus-delivered cIApIn1 small interfering rnA) partially resulted from accumulation of p53 protein, indicating cIApIn1 might inhibit the expression or accumulation of p53 (11). For loVo cells is known to express wild-type p53 (6), we investigated the role of p53 in the cIApIn1-related MDr in present study.…”

“…therefore, cIApIn1 conferring MDr in cancer cells via regulating the expression of mutant p53 is not comprehensive. More recently, li et al found that down-regulation of cIApIn1 by adenovirusdelivered small interfering rnA could result in enhanced expression of p53 protein in Hepg2 and sMMc-7721 cells that contained wild-type p53 gene (11). It seems reasonable that cIApIn1 mediated MDr in wild-type p53 loVo cells via inhibiting expression of p53 (30).…”

“…At 90-95% confluency, cells were washed twice with pBs and grown in 2 ml rpIM-1640 without antibiotics. Using lipofectamine™ 2000 reagent (Invitrogen, Inc., carlsbad, cA, UsA), 2 µg pcDnA3.1 (Invitrogen) which included the full-length cDnA for cIApIn1, or psip53 small interfering rnA (sirnA) plasmids was transfected into loVo cells, respectively, and 2 µg psicIApIn1 sirnA plasmids were transfected into loVo/Adr cells, as described previously (4,11). the cells that had been transfected with pcDnA3.1 vector alone or psilencer™ 3.1-H1 neo vector alone served as negative control.…”

RNA Interference for Tumor Therapy

“…In recent years, many studies on the relationship www.intechopen.com between CIAPIN1 and tumor formation showed that CIAPIN1 expression was increased significantly in HCC, gastric cancer and other malignant tumor tissues (Ida et al, 2007;. Li (Li et al, 2008) used adenovirus-mediated RNAi to knock out CIAPIN1 in HCC cells and found that CIAPIN1 gene expression in HCC cells was down-regulated, where cells were prevented from entering phase S and cell proliferation was inhibited. Eight weeks after injection of adenovirus/siRNA between transplanted tumor tissues, the tumor size was only one-sixth of the control group, and pathological sections showed apoptotic cells in tumor tissues.…”