Volume 16, Number 2, June 2004

Antisense Oligonucleotide Therapy for Oral Squamous Cell Carcinoma in a Nude Mouse Model

Cheng-Hsien Wu,1,2 Hsi-Feng Tu,1,2 Jenny Fong,2 Che-Shoa Chang,1,2 Shou-Yen Kao1,2

1Oral & Maxillofacial Surgery, Department of Dentistry, Taipei Veterans General Hospital, and 2School of Dentistry, National Yang-Ming University, Taipei, Taiwan

Abstract

Objective: Oral squamous cell carcinoma is the fifth most common malignancy among Taiwanese men. Telomerase reactivation is thought to be related to unregulated growth of tumour cells. Telomerase activity in oral squamous cell carcinoma cells, but not in normal somatic cells, suggest that it is a potential target for therapy. In this study, we used antisense oligonucleotide, which acts against human telomerase RNA and telomerase-associated protein 1, to investigate the connection between telomerase inhibition and cancer therapy.
Materials and Methods: An in vivo tumour model was established with athymic nude mice and oral squamous cell carcinoma cell line-KB. Oligonucleotides with anti-human telomerase RNA and anti-telomerase-associated protein 1 were injected intratumourally twice a week for 2 weeks. The antiproliferative effect was measured by changes in tumour volume, and a telomeric repeat amplification protocol was used to determine telomerase activity.
Results: Xenografted oral squamous cell carcinoma cells were established 3 weeks after inoculation. There were no statistically significant differences between the treatment and control groups in tumour volume change or telomerase activity.
Conclusions: In this in vivo study, we successfully established an oral cancer cell line in an animal model. A high degree of telomerase activity was noted among the oral cancer cells. Antisense oligonucleotide use had a mild suppressive effect on tumour growth and telomerase activity. However, we could not define its therapeutic significance. Further fine-tuning of administration routes, types of vectors for antisense oligomers, targets for antisense oligomers, and different oral cancer cell lines may improve the results of anti-telomerase therapy.


Key words: Antisense oligonucleotides, Oral cancer, Telomerase

Asian J Oral Maxillofac Surg. 2004;16:109-115.
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