Effect of combined antisense oligodeoxynucleotides directed against the human papillomavirus type 16 on cervical carcinoma cells.
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.
Márquez-Gutiérrez
Miguel A
MA
Laboratorio de Terapia Génica, Departamento de Genética y Biología Molecular, CINVESTAV, México DF, México.
Benítez-Hess
María L
ML
DiPaolo
Joseph A
JA
Alvarez-Salas
Luis M
LM
D002277:Carcinoma / Q000628:therapy* / Q000821:virology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000254:growth & development*; D006801:Humans; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use*; D012333:RNA, Messenger; D012367:RNA, Viral; D002583:Uterine Cervical Neoplasms / Q000628:therapy* / Q000821:virology*
D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D012367:RNA, Viral