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Arch Med Res. 2007 Oct;38(7):730-8. Epub 2007 Jul 26.

Effect of combined antisense oligodeoxynucleotides directed against the human papillomavirus type 16 on cervical carcinoma cells.

Author information

1
Laboratorio de Terapia Génica, Departamento de Genética y Biología Molecular, CINVESTAV, México DF, México.

Abstract

BACKGROUND:

Cervical cancer is highly associated with human papillomavirus (HPV) E6 and E7 gene expression. We have previously reported two antisense oligodeoxynucleotides (AS-ODNs) directed against adjacent targets within the HPV-16 E6/E7 mRNA (419 and 434), each able to downregulate HPV-16 E6/E7 mRNA in vitro and in vivo and to specifically inhibit tumor cell growth in culture and animal models.

METHODS:

Towards potential clinical application and improved in vivo performance, we analyzed the effect of the combined treatment of 419-434 AS-ODNs on the anchorage independent growth (AIG) of HPV-16-positive cervical carcinoma cell lines.

RESULTS:

We found similar responses between combined 419-434 and individual AS-ODNs treatments in RNaseH assays, cell uptake, and in vivo degradation of HPV-16 E6/E7 transcripts. Moreover, the combined use of 419-434 AS-ODNs resulted in additive AIG inhibition of CaSki and SiHa cells, similar to that obtained with equivalent doses of the individual AS-ODNs.

CONCLUSIONS:

By using a combined treatment, it may be possible to overcome the potential mutations frequently reported within HPV-16 genome, thus improving the potential application of 419 and 434 AS-ODNs as a therapeutic alternative for cervical cancer.

PMID:
17845891
DOI:
10.1016/j.arcmed.2007.04.011
[Indexed for MEDLINE]

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