Attenuated Salmonella carrying plasmid co-expressing HPV16 L1 and siRNA-E6 for cervical cancer therapy

Sci Rep. 2021 Oct 11;11(1):20083. doi: 10.1038/s41598-021-99425-3.

Abstract

Human papillomavirus (HPV) infection is the major etiological factor for cervical cancer. HPV prophylactic vaccines based on L1 virus-like particles have been considered as an effective prevention method. However, existing recombination vaccines are too expensive for developing countries. DNA vaccines might be a lower-cost and effective alternative. In this study, a plasmid (pcDNA3.1-HPV16-L1) and a co-expressing plasmid (pcDNA3.1-HPV16-L1-siE6) carried by attenuated Salmonella were constructed and their prevention and treatment effect on cervical cancer were observed, respectively. The results showed that pcDNA3.1-HPV16-L1 carried by attenuated Salmonella could induce the production of HPV16-L1 antibodies, IL-2 and INF-γ in mice serum, which presented its prevention effect on HPV. Subsequently, E6 and E7 gene silencing by pCG-siE6 inhibited the growth of cervical cancer both in vitro and in vivo. Furthermore, L1 up-regulation and E6/E7 down-regulation caused by co-expressing plasmid (pcDNA3.1-HPV16-L1-siE6) contributed to a significant anti-tumor effect on the mice. This study suggests that pcDNA3.1-HPV16-L1-siE6 carried by attenuated Salmonella has a synergistic effect of immune regulation and RNA interference in cervical cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Capsid Proteins / genetics*
  • Cell Proliferation
  • Female
  • Human papillomavirus 16 / genetics*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Oncogene Proteins, Viral / genetics*
  • Papillomavirus E7 Proteins / antagonists & inhibitors*
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / virology
  • Plasmids / administration & dosage*
  • Plasmids / genetics
  • RNA, Small Interfering / genetics*
  • Salmonella typhimurium / genetics*
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / therapy*
  • Uterine Cervical Neoplasms / virology
  • Xenograft Model Antitumor Assays

Substances

  • Capsid Proteins
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • RNA, Small Interfering
  • L1 protein, Human papillomavirus type 16