title: SiRNA-mediated survivin inhibition enhances chemo- or radiosensivity of colorectal cancer cells in tumor-bearing nude mice.
abstract: OBJECTIVE
  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.
authors: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China. xiaoyuanchu55@yahoo.com.cn
authors: Xiaoyuan
authors: X
authors: Chu
authors: Longbang
authors: L
authors: Chen
authors: Jinghua
authors: J
authors: Wang
authors: Xiaoxiang
authors: X
authors: Guan
authors: Huaicheng
authors: H
authors: Geng
authors: Qun
authors: Q
authors: Zhang
authors: Haizhu
authors: H
authors: Song
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D010957:Plasmids; D034741:RNA, Small Interfering / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000235:genetics; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D037941:Silencer Elements, Transcriptional / Q000235:genetics; D000077022:Survivin; D014407:Tumor Cells, Cultured
chemical_list: C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000077022:Survivin