Growth inhibition of cervical tumor cells by antisense oligodeoxynucleotides directed to the human papillomavirus type 16 E6 gene

Antisense Nucleic Acid Drug Dev. 1999 Oct;9(5):441-50. doi: 10.1089/oli.1.1999.9.441.

Abstract

Human papillomavirus type 16 (HPV-16) is the HPV type most frequently associated with cervical carcinomas. Based on our previous research with anti-HPV ribozymes, we developed a 16-nucleotide antisense oligodeoxynucleotide (AntiE6) able to direct RNase H activity on full-length HPV-16 E6/E7 mRNA. Although the precise mechanism is not completely understood, addition of 50 microM AntiE6 oligodeoxynucleotide in sterile water caused a significant decrease in the growth rate of CaSki and QGU cervical tumor cell lines. In contrast, addition of a mismatched mutant oligodeoxynucleotide (M7) did not affect cell growth after 72 hours. Treatment with AntiE6 resulted in down-regulation of E6/E7 mRNA and an increase in p53 levels in QGU cells. AntiE6 was also able to (>70%) inhibit significantly growth of transplanted cervical tumors in nude mice after 2 weeks treatment using constant delivery by osmotic pumps. These results indicate that the AntiE6 antisense oligodeoxynucleotides can act as a therapeutic agent against cervical carcinomas.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Division / drug effects*
  • DNA Primers
  • Female
  • Genes, p53
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Oligonucleotides, Antisense / pharmacology*
  • Oncogene Proteins, Viral / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins*
  • Ribonuclease H / metabolism
  • Tumor Cells, Cultured
  • Up-Regulation
  • Uterine Cervical Neoplasms / pathology*

Substances

  • DNA Primers
  • E6 protein, Human papillomavirus type 16
  • Oligonucleotides, Antisense
  • Oncogene Proteins, Viral
  • RNA, Messenger
  • Repressor Proteins
  • Ribonuclease H