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Enhancement of Cisplatin Sensitivity in Squamous Cell Carcinoma of the Head and Neck Transfected With a Survivin Antisense Gene
Hiromi Kojima, MD;
Minoru Iida, MD;
Yuichirou Yaguchi, MD;
Rie Suzuki, MD;
Norihiko Hayashi, MD;
Hiroshi Moriyama, MD;
Yoshinobu Manome, MD
Arch Otolaryngol Head Neck Surg. 2006;132:682-685.
Objective To study a new method for treating squamous cell carcinoma of the head and neck using a survivin antisense gene.
Design 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.
Setting In vitro and in vivo study of head and neck cancer cell line KB.
Subjects Male, 5-week-old BALB/c nude mice.
Main Outcome Measures 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.
Conclusion 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.
Author Affiliations: Departments of Otorhinolaryngology (Drs Kojima, Iida, Yaguchi, Suzuki, and Moriyama) and Urology (Dr Hayashi), and Division of Molecular Cell Biology, Institute of DNA Medicine (Dr Manome), Jikei University School of Medicine, Tokyo, Japan.
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