Therapeutic effect of oncolytic adenovirus expressing relaxin in radioresistant oral squamous cell carcinoma.
Radioresistance is one of the main determinants of treatment outcome in oral squamous cell carcinoma (OSCC), and treatment of radioresistant OSCC is difficult due to cross resistance to other conventional treatments. We aimed to identify whether genetically modified oncolytic adenovirus expressing relaxin (RLX), which affects collagen metabolism, can effectively inhibit growth of the radioresistant OSCC. Therapeutic effect of oncolytic adenovirus was compared between radiosensitive and radioresistant OSCC cell lines in vitro and in vivo, and spread of adenovirus throughout the tumor mass was verified by immunohistochemistry (IHC). Oncolytic adenovirus effectively killed cancer cells and there was no significant difference in the cytotoxic effect between radiosensitive and radioresistant OSCC cell lines. In animal experiments, the adenovirus significantly reduced the size of tumor, and there was no significant difference between radiosensitive and radioresistant OSCC. In IHC, RLX expressing adenovirus showed better proliferation and eliminated collagens more effectively compared to RLX nonexpressing adenovirus. These findings suggested that genetically modified oncolytic adenovirus can effectively inhibit growth of the radioresistant OSCC and might be a new therapeutic option in radioresistant OSCC.
Department of Otolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
Sei Young
SY
Lee
Haeng Ran
HR
Park
Junghoon
J
Rhee
Young Min
YM
Park
Se-Heon
SH
Kim
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000556:secondary; D045744:Cell Line, Tumor / Q000528:radiation effects* / Q000821:virology; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000502:physiology*; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000473:pathology*; D016297:Mutagenesis, Site-Directed; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D011836:Radiation Tolerance; D012065:Relaxin / Q000235:genetics / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D014062:Tongue Neoplasms / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D012065:Relaxin