Inhibition of cervical cancer cell growth in vitro and in vivo with dual shRNAs

Cancer Gene Ther. 2011 Mar;18(3):219-27. doi: 10.1038/cgt.2010.72. Epub 2010 Nov 19.

Abstract

RNA interference (RNAi)-based gene silencing is widely used in laboratories for gene function studies and also holds a great promise for developing treatments for diseases. However, in vivo delivery of RNAi therapy remains a key issue. Lentiviral vectors have been employed for stable gene transfer and gene therapy and therefore are expected to deliver a stable and durable RNAi therapy. But this does not seem to be true in some disease models. Here, we showed that lentivirus delivered short-hairpin RNA (shRNA) against human papillomavirus (HPV) E6/E7 oncogenes were effective for only 2 weeks in a cervical cancer model. However, using this vector to carry two copies of the same shRNA or two shRNAs targeting at two different but closely related genes (HPV E6 and vascular endothelial growth factor) was more effective at silencing the gene targets and inhibiting cell or even tumor growth than their single shRNA counterparts. The cancer cells treated with dual shRNA were also more sensitive to chemotherapeutic drugs than single shRNA-treated cells. These results suggest that a multi-shRNA strategy may be a more attractive approach for developing an RNAi therapy for this cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Proliferation
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Dosage*
  • Gene Expression Regulation, Neoplastic / genetics
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Lentivirus / genetics
  • Lentivirus / metabolism
  • Mice
  • Mice, Knockout
  • Oncogene Proteins, Viral / antagonists & inhibitors
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism
  • RNA Interference
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / therapy
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 18
  • E7 protein, Human papillomavirus type 18
  • Oncogene Proteins, Viral
  • RNA, Small Interfering
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A