Enhancement of Cisplatin sensitivity in squamous cell carcinoma of the head and neck transfected with a survivin antisense gene

Arch Otolaryngol Head Neck Surg. 2006 Jun;132(6):682-5. doi: 10.1001/archotol.132.6.682.

Abstract

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.

MeSH terms

  • Adenoviridae
  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Cisplatin / pharmacology*
  • Cysteine Proteinase Inhibitors / genetics
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Genetic Therapy / methods*
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / pathology
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / pharmacology*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / pharmacology*
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacology*
  • Survivin
  • Transfection

Substances

  • BIRC5 protein, human
  • Cysteine Proteinase Inhibitors
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Oligonucleotides, Antisense
  • Survivin
  • Cisplatin