title: Therapeutic silencing of HPV 16 E7 by systemic administration of siRNA-neutral DOPC nanoliposome in a murine cervical cancer model with obesity.
abstract: OBJECTIVE
  To evaluate the effectiveness of a neutral DOPC nanoliposome system for the delivery of siRNA to tumor cells in an obese murine cervical cancer model.
  
  
  METHODS
  In vitro silencing of E6-E7 mRNA and E7 protein using siRNAE6 or siRNAE7 was analyzed in TC-1 cells by RT-PCR and Western blot. Silencing and antitumor capacities of siRNAE7-DOPC-nanoparticles (NP) were tested in vivo in both normal and obese mice using qPCR. These NPs were administered twice a week for 15 days and tumor volume and weight were recorded.
  
  
  RESULTS
  Levels of in vitro E6-E7 silencing were 90% for mRNA and 60% for protein when siRNAE7 was used. On the other hand when siRNAE6 was used, the levels of silencing were 50% for E6-E7 mRNA and only 20% for protein. In vivo E7 mRNA silencing by siRNAE7-DOPC-NP was similar (60%) in both non-obese and obese mouse models. The therapeutic study showed a 65% decrease in tumor volume and a 57% reduction in tumor weight as compared to the control groups.
  
  
  CONCLUSIONS
  There was no negative impact of obesity on the antitumor activity of siRNA-DOPC-NP in obese mice.
authors: Centro de Investigación y de Estudios Avanzados del IPN, Unidad Monterrey, Nuevo León, Mexico.
authors: Hector
authors: H
authors: Chapoy-Villanueva
authors: Ivonne
authors: I
authors: Martinez-Carlin
authors: G
authors: G
authors: Lopez-Berestein
authors: Arturo
authors: A
authors: Chavez-Reyes
mesh_terms: D000818:Animals; D005260:Female; D020868:Gene Silencing; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D009765:Obesity / Q000150:complications*; D050725:Papillomavirus E7 Proteins / Q000235:genetics*; D010713:Phosphatidylcholines / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000628:therapy* / Q000821:virology
chemical_list: D008081:Liposomes; D050725:Papillomavirus E7 Proteins; D010713:Phosphatidylcholines; D034741:RNA, Small Interfering; C059731:oncogene protein E7, Human papillomavirus type 16; C017251:1,2-oleoylphosphatidylcholine