Differentiation of human nasopharyngeal carcinoma xenografts and repression of telomerase activity induced by arsenic trioxide.

ABSTRACT

BACKGROUND: Arsenic trioxide (As2O3) induced apoptosis and differentiation of acute promyelocytic leukaemia. A few in vivo experimental investigations of its efficacy in solid tumours have been done. This study was designed to explore the differentiation-inducing effect, and the possible mechanisms involved, of As2O3 on human nasopharyngeal carcinoma CSNE-1 xenografts. METHODS: Nasopharyngeal carcinoma cell CSNE-1 was established as a xenograft in nude mice. The tumour-bearing mice were treated with As2O3 at a dose of 5 mg/kg/day. To assess tumour differentiation, tumour growth was observed and histological changes were analysed under light and electron microscopy. Expression of latent membrane protein 1 (LMP1) and cytokeratin 4 (CK4) was determined by immunohistochemistry. A PCR-based telomeric repeat amplification protocol assay (TRAP-ELISA) was used to measure telomerase activity. RESULTS: The xenografts underwent differentiation. LMP 1 of the cells decreased significantly and there was a pronounced decline in telomerase activity. CONCLUSION: As2O3 can inhibit xenograft growth and induce morphological and functional differentiation of CSNE-1 cells. The As2O3-induced differentiation was associated with downregulation of telomerase activity.