HSV-1 Infection Modulates the Radioresponse of a HPV16-positive Head and Neck Cancer Cell Line

Anticancer Res. 2016 Feb;36(2):565-74.

Abstract

Background: The combined effects of Human papillomavirus (HPV) and Herpes simplex type 1 (HSV-1) infections and their effects on cancer cell radioresistance are unexplored.

Materials and methods: An HPV16-positive hypopharyngeal carcinoma cell line (UD-SCC-2) was infected with wt-HSV-1 at low multiplicity of infection (MOI) and irradiated with 2 Gy at 24 h postinfection. Viability assays and quantitative reverse-transcriptase PCR for HPV16 E6, E7, nuclear factor kappa B1, B-cell CLL/lymphoma 2 (BCL2), and caspases 3, 8 and 9 at 24, and 72 h, as well as immunocytochemistry for BCL2, caspase 3, cyclin E, mouse double minute 2 homolog (MDM2), HSV-1 and Ki-67 were performed at 144 h postirradiation.

Results: At 144 h, cell viability was significantly lowered by irradiation only in uninfected cells. Infection combined with irradiation resulted in increased expression of E6, E7, BCL2 and NF-κB1 at 144 h. Simultaneously, E6 and E7 were down-regulated in non-irradiated infected cells. Irradiation and infection with 0.00001 MOI separately up-regulated caspase 3 but infection with 0.0001 MOI halved its expression in irradiated cells.

Conclusion: HSV-1 infection modulates radioresistance of HPV16-positive hypopharyngeal carcinoma cells.

Keywords: HSV-1; head and neck cancer; herpes simplex virus; human papillomavirus; irradiation; radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Carcinoma, Squamous Cell / virology
  • Gamma Rays*
  • Gene Expression Regulation, Viral / radiation effects
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / radiotherapy*
  • Head and Neck Neoplasms / virology
  • Herpesvirus 1, Human / radiation effects*
  • Human papillomavirus 16 / radiation effects*
  • Humans
  • Immunoenzyme Techniques
  • Mice
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / radiotherapy*
  • Papillomavirus Infections / virology
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Viral Load / radiation effects*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • RNA, Messenger
  • Viral Proteins