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. 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.