Growth inhibition and chemo-radiosensitization of esophageal squamous cell carcinoma by survivin-shRNA lentivirus transfection

摘要

Esophageal cancer is one of the most common types of cancer worldwide, and it has a poor prognosis. Chemo-radiotherapy resistance and cancer relapse are among the most difficult issues in its treatment. Identifying the underlying molecular mechanisms is critical for developing novel therapies. Survivin has been previously suggested to be overexpressed in esophageal cancer cells. The present study identified that down-regulation of survivin sensitized esophageal cancer cells to chemo-radiotherapy. Consistent with previous studies, the present study indicated that survivin was overexpressed in 4 esophageal squamous carcinoma cell lines. Short hairpin RNA delivered by lentivirus successfully knocked down survivin in these cancer cell lines. Consequently, down-regulation of survivin impaired their colony-forming, migratory and invasive capabilities, while the overexpression of survivin in normal human esophagus epithelial cells improved their resistance to cisplatin, paclitaxel and radiation. Survivin knockdown induced apoptosis in esophageal cancer KYSE-150 and ECA-109 cell lines when exposed to the aforementioned chemo-radiotherapy treatments. These results indicate that survivin expression sustains growth in esophageal cancer cells, and confers resistance to chemo-radiotherapy. Targeted survivin ablation may be a promising strategy against esophageal tumor relapse and chemo-radioresistance.