title: 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).
authors.affiliation: a Department of Otolaryngology , Head and Neck Surgery ;
authors.forename: Arunkumar
authors.initials: A
authors.lastname: Anandharaj
authors.affiliation: a Department of Otolaryngology , Head and Neck Surgery ;|b Feist-Weiller Cancer Center ;
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Ekshyyan
authors.affiliation: c Department of Microbiology and Immunology ;
authors.forename: Yali
authors.initials: Y
authors.lastname: Jia
authors.affiliation: a Department of Otolaryngology , Head and Neck Surgery ;|b Feist-Weiller Cancer Center ;
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Rong
authors.affiliation: d Department of Molecular and Cellular Physiology , LSU Health - Shreveport , Shreveport , LA , USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Harrison
authors.affiliation: b Feist-Weiller Cancer Center ;
authors.forename: Runhua
authors.initials: R
authors.lastname: Shi
authors.affiliation: b Feist-Weiller Cancer Center ;|c Department of Microbiology and Immunology ;
authors.forename: Rona S
authors.initials: RS
authors.lastname: Scott
authors.affiliation: a Department of Otolaryngology , Head and Neck Surgery ;|b Feist-Weiller Cancer Center ;
authors.forename: Cherie-Ann O
authors.initials: CA
authors.lastname: Nathan
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy / Q000821:virology*; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005814:Genes, Viral; D006258:Head and Neck Neoplasms / Q000532:radiotherapy / Q000821:virology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D009857:Oncogenes; D030361:Papillomavirus Infections / Q000150:complications*; D012367:RNA, Viral / Q000378:metabolism; D064424:Tobacco Use / Q000009:adverse effects*
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral
keywords: Squamous cell carcinoma; cell cycle; clonogenic assay; co-infection; radiation; radiosensitivity; senescence