Enhancement of Cisplatin sensitivity in squamous cell carcinoma of the head and neck transfected with a survivin antisense gene.
OBJECTIVE
To study a new method for treating squamous cell carcinoma of the head and neck using a survivin antisense gene.


METHODS
An adenoviral vector encoding surviving antisense was used for in vitro and in vivo experiments. KB cells were treated with pAd.CMV[cytomegalovirus]-antisurvivin. Western blot analysis, in vitro cytotoxic assay, and in vivo experiment were performed.


METHODS
In vitro and in vivo study of head and neck cancer cell line KB.


METHODS
Male, 5-week-old BALB/c nude mice.


METHODS
Expression of survivin was assessed using Western blot analysis. The effect of antisurvivin to KB cells was measured by cytotoxic assay (in vitro) and tumor volume (in vivo).


RESULTS
In the in vitro experiments, transduction of the survivin antisense gene caused a nearly 12-fold increase in the sensitivity of KB cells to cisplatin, as reflected by the 50% inhibitory concentration. In in vivo experiments in nude mice, tumor growth was more inhibited by the combination of cisplatin and survivin antisense gene transduction compared with either alone.


CONCLUSIONS
These findings suggest that survivin targeting with adenoviral antisense vectors might be used for selective therapy of squamous cell carcinomas of the head and neck.
Kojima
Hiromi
H
Department of Otorhinolaryngology, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, Japan. Kojimah@jikei.ac.jp
Iida
Minoru
M
Yaguchi
Yuichirou
Y
Suzuki
Rie
R
Hayashi
Norihiko
N
Moriyama
Hiroshi
H
Manome
Yoshinobu
Y
D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics / Q000494:pharmacology*; D015316:Genetic Therapy / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D000077022:Survivin; D014162:Transfection
C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D000077022:Survivin; D002945:Cisplatin