Plasmid-based E6-specific siRNA and co-expression of wild-type p53 suppresses the growth of cervical cancer in vitro and in vivo

Cancer Lett. 2013 Jul 10;335(1):242-50. doi: 10.1016/j.canlet.2013.02.034. Epub 2013 Feb 20.

Abstract

The E6 protein of the oncogenic HPV-16 functions by interfering with the normal cell cycle control mechanisms, particularly those controlled by p53. In this study, we developed a dual expression plasmid that coexpressed-E6-specific siRNA and wild type p53, and to evaluate its effects on cervical cancer growth. We found that simultaneous expression of pSi-E6-P53 caused a robust suppression of tumor growth when compared to the controls either E6-specific siRNA or p53 alone. In conclusion, our findings demonstrate that a combined strategy of co-expressed E6-specific siRNA and p53 synergistically and more effectively suppressed cervical tumor growth when compared with single treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Cell Survival
  • Female
  • Gene Expression
  • Gene Knockdown Techniques
  • Genetic Therapy / methods
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Oncogene Proteins, Viral / genetics*
  • Oncogene Proteins, Viral / metabolism
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / therapy*
  • Plasmids / genetics
  • RNA, Small Interfering / genetics*
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Salmonella typhimurium / genetics
  • Transformation, Bacterial
  • Tumor Burden
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy*

Substances

  • Apoptosis Regulatory Proteins
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • RNA, Small Interfering
  • Repressor Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53