PMID- 21443101
OWN - NLM
STAT- MEDLINE
DCOM- 20110421
LR  - 20181201
IS  - 0172-6390 (Print)
IS  - 0172-6390 (Linking)
VI  - 57
IP  - 104
DP  - 2010 Nov-Dec
TI  - SiRNA-mediated survivin inhibition enhances chemo- or radiosensivity of 
      colorectal cancer cells in tumor-bearing nude mice.
PG  - 1445-52
AB  - BACKGROUND/AIMS: Previously, we have reported that siRNA-mediated survivin 
      inhibition could enhance in vitro chemo- or radiosensitivity of colorectal cancer 
      (CRC) cells. The aim of this study was to investigate whether that small 
      interfering RNA (siRNA) targeting survivin could enhance in vivo chemo- or 
      radiosensitivity of colorectal cancer cells. METHODS: pSilencer4.1-shRNA 
      targeting survivin (pSilencer4.1-s) and pSilencer4.1-NC (negative control) 
      vectors were previously constructed by us. Two colorectal cancer cell lines (LoVo 
      or HCT-8) were collected and used for forming subcutaneous tumors in nude mice. 
      Then, the tumors were intratumorally injected with pSilencer4.1-s or 
      pSilencer4.1-NC vectors combined with chemotherapy (5-FU) or radiotherapy (6Gy). 
      Firstly, the expression of survivin mRNA and protein in tumors treated with 
      pSilencer4.1-s or pSilencer4.1-NC alone was detected by RT-PCR and Western 
      blotting or immunohistochemistry assays. Next, the tumor volumes were recorded. 
      The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 
      assay was performed to detect apoptosis of tumor cells and the activity of 
      caspase-3 was detected. RESULTS: The expression of survivin mRNA and protein in 
      tumor tissues treated with pSilencer4.1-s was significantly downregulated (p < 
      0.05). The immunostaining of survivin protein was also significantly weaker in 
      tumor tissues treated with pSilencer4.1-s. Moreover, the volumes of the nude mice 
      treated with pSilencer4.1-s and chemo- or radiotherapy decreased markedly 
      compared with those of the mock- or pSilencer4.1NC-treated control combined with 
      chemo- or radiotherapy. The apoptosis of tumor tissue cells treated with 
      pSilencer4.1-s and chemo- or radiotherapy could be significantly increased 
      compared with the mock- or pSilencer4.1-NC-treated control combined with chemo- 
      or radiotherapy (p < 0.05), which might be associated with the active Caspase-3 
      pathway. CONCLUSIONS: siRNA-mediated survivin inhibition could enhance in vivo 
      chemo- or radiosensitivity of CRC cells. Accordingly, the survivin gene might be 
      a potential target for the chemoradiotherapy of CRC.
FAU - Chu, Xiaoyuan
AU  - Chu X
AD  - Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing 
      University, Nanjing 210002, China. xiaoyuanchu55@yahoo.com.cn
FAU - Chen, Longbang
AU  - Chen L
FAU - Wang, Jinghua
AU  - Wang J
FAU - Guan, Xiaoxiang
AU  - Guan X
FAU - Geng, Huaicheng
AU  - Geng H
FAU - Zhang, Qun
AU  - Zhang Q
FAU - Song, Haizhu
AU  - Song H
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Hepatogastroenterology
JT  - Hepato-gastroenterology
JID - 8007849
RN  - 0 (Birc5 protein, mouse)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Repressor Proteins)
RN  - 0 (Survivin)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Apoptosis/genetics
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Colorectal Neoplasms/*drug therapy/genetics/*radiotherapy
MH  - Immunoenzyme Techniques
MH  - In Situ Nick-End Labeling
MH  - Inhibitor of Apoptosis Proteins/*antagonists & inhibitors/genetics
MH  - Mice
MH  - Mice, Nude
MH  - Plasmids
MH  - RNA, Small Interfering/*pharmacology
MH  - Radiation Tolerance/genetics
MH  - Repressor Proteins/*antagonists & inhibitors/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Silencer Elements, Transcriptional/genetics
MH  - Survivin
MH  - Tumor Cells, Cultured
EDAT- 2011/03/30 06:00
MHDA- 2011/04/22 06:00
CRDT- 2011/03/30 06:00
PHST- 2011/03/30 06:00 [entrez]
PHST- 2011/03/30 06:00 [pubmed]
PHST- 2011/04/22 06:00 [medline]
PST - ppublish
SO  - Hepatogastroenterology. 2010 Nov-Dec;57(104):1445-52.