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


CONCLUSIONS
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.
Du
Caiwen
C
Shantou University Medical College, Shantou, Guangdong 515031, China.
Li
Derui
D
Lin
Yingcheng
Y
Wu
Mingyao
M
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D007150:Immunohistochemistry; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010087:Oxides / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D019098:Telomerase / Q000037:antagonists & inhibitors*; D014183:Transplantation, Heterologous / Q000473:pathology*
D001152:Arsenicals; D010087:Oxides; D019098:Telomerase; D000077237:Arsenic Trioxide