Lentivirus-mediated gene therapy by suppressing survivin in BALB/c nude mice bearing oral squamous cell carcinoma

Cancer Biol Ther. 2006 Apr;5(4):435-40. doi: 10.4161/cbt.5.4.2542. Epub 2006 Apr 22.


Despite advances in surgery, radiotherapy, and chemotherapy, the long-term survival rates with oral squamous cell carcinoma (OSCC) have not significantly improved. Gene therapy for OSCC is currently under investigation in clinical trials. Lentivirus vector is considered to be a promising gene delivery tool, but their value in cancer gene therapy has not been studied thoroughly. Survivin is overexpressed in OSCC, making it a promising target for gene therapy. This study was conducted to determine whether lentivirus-mediated gene therapy by suppressing survivin could be exploited in the treatment of OSCC. A lentivirus vector encoding short hairpin RNA (shRNA) targeting survivin was constructed and transfected into KB cells in vitro. The results showed that survivin was persistently and markedly reduced by lentivirus-mediated RNA interference (RNAi); the growth of KB cells was decreased by 34.2% on day 5; the apoptosis rate induced by vincristine (VCR) was increased by 29.8% and caspase-3 activity was also significantly increased; the IC(50) value of adriamycin (ADM) were 0.09 mug/ml, which indicated that survivin-knockout KB cells were 2.1 times more susceptible to ADM than the control; the clonogenic survival rate at 6 Gy of X ray was 3.7%, less than 15.3% of the control. In the xenograft model, the development of tumors as well as the growth of established tumors was inhibited by transfection of lentivirus. Our study indicates that lentivirus-mediated gene therapy is an attractive strategy in the treatment of OSCC and justifies the use of lentivirus in cancer gene therapy studies.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / therapy*
  • Caspase 3 / metabolism
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Lentivirus / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Mouth Neoplasms / therapy*
  • Neoplasm Transplantation
  • Neoplasms / genetics*
  • RNA Interference
  • Repressor Proteins
  • Survivin


  • Birc5 protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Repressor Proteins
  • Survivin
  • Caspase 3