Inhibition of cervical cancer cell growth in vitro and in vivo with lentiviral-vector delivered short hairpin RNA targeting human papillomavirus E6 and E7 oncogenes

Cancer Gene Ther. 2006 Nov;13(11):1023-32. doi: 10.1038/sj.cgt.7700971. Epub 2006 Jun 30.


In this study, we investigated the suppressive effect of a short hairpin RNA delivered by a lentiviral vector (LV-shRNA) against human papillomavirus (HPV) type 18 E6 on the expression of the oncogenes E6 and E7 in cervical cancer HeLa cells both in vitro and in vivo. The LV-shRNA effectively delivered the shRNA to HeLa cells and lead to a dose-dependent reduction of E7 protein and the stabilization of E6 target proteins, p53 and p21. Low-dose infection of HeLa cells with LV-shRNA caused reduced cell growth and the induction of senescence, whereas a high-dose infection resulted in specific cell death via apoptosis. Transplant of HeLa cells infected with a low dose of LV-shRNA into Rag-/- mice significantly reduced the tumor weight, whereas transplant of cells infected with a high dose resulted in a complete loss of tumor growth. Systemic delivery of LV-shRNA into mice with established HeLa cell lung metastases led to a significant reduction in the number of tumor nodules. Our data collectively suggest that lentiviral delivery is an effective way to achieve stable suppression of E6/E7 oncogene expression and induce inhibition of tumor growth both in vitro and in vivo. These results encourage further investigation of this form of RNA interference as a promising treatment for cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Blotting, Northern
  • Blotting, Western
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Survival / genetics
  • Female
  • Gene Expression / genetics
  • Genetic Vectors / genetics
  • HeLa Cells
  • Humans
  • Lentivirus / genetics
  • Mice
  • Oncogene Proteins, Viral / genetics*
  • Oncogene Proteins, Viral / metabolism
  • Papillomavirus E7 Proteins
  • Polymerase Chain Reaction / methods
  • RNA Interference*
  • RNA, Small Interfering / genetics*
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / therapy*
  • Xenograft Model Antitumor Assays


  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • RNA, Small Interfering
  • Repressor Proteins
  • Tumor Suppressor Protein p53
  • oncogene protein E7, Human papillomavirus type 16
  • Caspase 3
  • Caspase 7