PMID- 19496189
OWN - NLM
STAT- MEDLINE
DCOM- 20090817
LR  - 20211020
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Print)
IS  - 1007-9327 (Linking)
VI  - 15
IP  - 21
DP  - 2009 Jun 7
TI  - Silencing of signal transducer and activator of transcription 3 expression by RNA 
      interference suppresses growth of human hepatocellular carcinoma in tumor-bearing 
      nude mice.
PG  - 2602-8
AB  - AIM: To explore the effect of silencing of signal transducer and activator of 
      transcription 3 (STAT3) expression by RNA interference (RNAi) on growth of human 
      hepatocellular carcinoma (HCC) in tumor-bearing nude mice in vivo. METHODS: To 
      construct the recombinant plasmid of pSilencer 3.0-H1-STAT3-siRNA-GFP 
      (pSH1-siRNA-STAT3) and establish the tumor-bearing nude mouse model of the HCC 
      cell line SMMC7721, we used intratumoral injection together with electroblotting 
      to transfect the recombinant plasmid pSH1-siRNA-STAT3 into the transplanted 
      tumor. The weight of the nude mice and tumor volumes were recorded. STAT3 gene 
      transcription was detected by semi-quantitative reverse transcription polymerase 
      chain reaction (RT-PCR). Level of protein expression and location of STAT3 were 
      determined by Western blotting and immunohistochemical staining. STAT3-related 
      genes such as survivin, c-myc, VEGF, p53 and caspase3 mRNA and protein expression 
      were detected in tumor tissues at the same time. The terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) assay was used to detect 
      apoptosis of tumor cells. RESULTS: The weight of the treated nude mice increased, 
      and the tumor volume decreased markedly compared with those of the mock-treated 
      and negative control groups (P < 0.01). The results of RT-PCR and Western 
      blotting showed that mRNA and protein levels of STAT3 declined markedly in the 
      treated group. The change in STAT3-related gene expression in tumor tissues at 
      the mRNA and protein level also varied, the expression of survivin, VEGF and 
      c-myc were obviously reduced, and expression of p53 and caspase3 increased (P < 
      0.01). Most of the tumor tissue cells in the treated group developed apoptosis 
      that was detected by TUNEL assay. CONCLUSION: Silencing of STAT3 expression by 
      RNAi significantly inhibits expression of STAT3 mRNA and protein, and suppresses 
      growth of human HCC in tumor-bearing nude mice. The mechanism may be related to 
      down-regulation of survivin, VEGF and c-myc and up-regulation of p53 and caspase3 
      expression. Accordingly, the STAT3 gene may act as an important and effective 
      target in gene therapy of HCC.
FAU - Li, Jing
AU  - Li J
AD  - Department of Gastroenterology, the First Hospital of Jilin University, 71 Xinmin 
      Avenue, Changchun 130021, Jilin Province, China.
FAU - Piao, Yun-Feng
AU  - Piao YF
FAU - Jiang, Zheng
AU  - Jiang Z
FAU - Chen, Li
AU  - Chen L
FAU - Sun, Hai-Bo
AU  - Sun HB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Birc5 protein, mouse)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (Repressor Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Survivin)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - *Carcinoma, Hepatocellular/genetics/metabolism/pathology
MH  - Caspase 3/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Gene Expression Regulation, Neoplastic
MH  - *Gene Silencing
MH  - Humans
MH  - Inhibitor of Apoptosis Proteins
MH  - *Liver Neoplasms/genetics/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - *Mice, Nude
MH  - Microtubule-Associated Proteins/genetics/metabolism
MH  - Neoplasm Transplantation
MH  - Proto-Oncogene Proteins c-myc/genetics/metabolism
MH  - RNA Interference
MH  - Repressor Proteins
MH  - *STAT3 Transcription Factor/genetics/metabolism
MH  - Survivin
MH  - Tumor Suppressor Protein p53/genetics/metabolism
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
PMC - PMC2691490
EDAT- 2009/06/06 09:00
MHDA- 2009/08/18 09:00
PMCR- 2009/06/07
CRDT- 2009/06/05 09:00
PHST- 2009/06/05 09:00 [entrez]
PHST- 2009/06/06 09:00 [pubmed]
PHST- 2009/08/18 09:00 [medline]
PHST- 2009/06/07 00:00 [pmc-release]
AID - 10.3748/wjg.15.2602 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2009 Jun 7;15(21):2602-8. doi: 10.3748/wjg.15.2602.