SiRNA-Mediated Survivin Inhibition Enhances Chemo- or Radiosensivity of Colorectal Cancer Cells in Tumor-Bearing Nude Mice

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 tells. 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 pSilencer4.1-NC-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.