EBV and not HPV sensitizes tobacco-associated head and neck cancer cell line FaDu to radiotherapy

Abstract

Conclusion EBV radiosensitized the p53 mutant tobacco associated head and neck cell line, FaDu.

Objectives In the head and neck, HPV is a major risk factor associated with tonsil and base of tongue cancers, while a majority of undifferentiated nasopharyngeal cancers are positive for EBV. Clinically, head and neck tumors positive for HPV or EBV are more radiosensitive than tumors associated with tobacco and alcohol. This study aimed to evaluate whether viral infections can sensitize tobacco-associated head and neck squamous cell carcinoma cell line that harbors multiple mutations, especially TP53, to radiotherapy. Method Four FaDu cell lines (vector control – FaDu-DN; FaDu expressing HPV16 E6/E7 – FaDu-HPV; FaDu infected with EBV – FaDu-EBV; and FaDu-HPV infected with EBV – FaDu-HE) were evaluated for their radiation sensitivity using clonogenic assay. Cell cycle, protein expression, apoptosis, and cellular senescence were analyzed.

Results FaDu-EBV and FaDu-HE exhibited significantly increased radiosensitivity in comparison with the control cell line. Radiation-induced cell cycle arrest was altered in all cell lines expressing viral genes. The observed distribution of cells at G1 and S phases was associated with a significant increase in expression of p21 protein along with decreased levels of pAKT/AKT and pERK/ERK ratio (p < 0.05) and increased cellular senescence (p < 0.05).

Keywords:

• Squamous cell carcinoma
• radiation
• radiosensitivity
• clonogenic assay
• co-infection
• cell cycle
• senescence

Acknowledgments

Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number P30GM110703, by Public Health Service grant GM103433 (to the Center of Molecular and Tumor Virology) from the National Institute of General Medical Sciences and a Feist-Weiller Cancer Center IDEA Award (to C-AON and RSS). This study was presented at CORLAS meeting – 2015.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.