[Combination of adenovirus p16(INK4A) gene therapy and ionizing radiation for laryngeal squamous cell carcinoma].
OBJECTIVE
To assess the anti-tumor effect of p16(INK4A) gene transfer and the combined effect of this gene therapy and ionizing radiation in the treatment of laryngeal squamous cell carcinoma.


METHODS
A Complete p16(INK4A) gene was inserted into a replication-defective recombinant adenovirus, and the tumor cells were infected with Adenovinus-p16 (Ad-p16) and irradiated with X-rays. Confirmation of P16(INK4A) protein expression after Ad-p16 infection was performed by Western blotting. The therapeutic effects were evaluated both in vitro and in vivo.


RESULTS
The replication-defective recombinant adenovirus could direct a high level of P16INK4A protein expression in laryngeal squamous cell carcinoma. Studies both in vitro and in vivo demonstrated that Ad-p16 treatment significantly inhibited the cell growth and the established tumors in mude mice when compared with the control treatments (P < 0.05). The combination of Ad-p16 and radiation group resulted in greater inhibition of tumor growth, compared with any other treatment groups and controls (P < 0.05). No significant difference was observed between Adenovirus-LacZ (Ad-LacZ) and PBS groups.


CONCLUSIONS
These results demonstrate a significant antitumor effect of Ad-p16 against human laryngeal squamous cell carcinoma and also demonstrate for the first time a combined effect of radiation and Ad-p16 gene transfer in p16 deficient human laryngeal squamous cell carcinoma.
Fu
Yan-jun
YJ
Department of Otolaryngology, West China Hospital, Sichuan University, Chengdu 610041, China.
Liu
Shi-xi
SX
Xian
Jun-ming
JM
D000256:Adenoviridae; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D019942:Genes, p16; D015316:Genetic Therapy / Q000379:methods*; D007822:Laryngeal Neoplasms / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D018714:Radiotherapy, Adjuvant; D014162:Transfection; D014407:Tumor Cells, Cultured
D019941:Cyclin-Dependent Kinase Inhibitor p16