Inhibition of growth of human nasopharyngeal cancer xenografts in SCID mice by arsenic trioxide.
OBJECTIVE
It is known that arsenic trioxide (As2O3) can induce clinical remission in patients suffering from acute promyelocytic leukemia. It has been suggested that the agent might also be effective against other malignancies. This study was done to explore the efficacy of As2O3 in the treatment of human nasopharyngeal cancer xenografts in SCID (severe combined immunodeficiency) mice.


METHODS
Human nasopharyngeal cancer cells from the CSNE-1 cell line were implanted subcutaneously into SCID mice to produce tumors. The tumor inhibitory rate in vivo was assessed after intraperitoneal administration of As2O3. Histopathological changes in the tumor tissues and the toxicity of As2O3 to the liver, heart and kidneys of the host mice were also investigated.


RESULTS
At doses of 1 mg/kg and 5 mg/kg As2O3 induced apoptosis in nasopharyngeal carcinoma cells. At 5 mg/kg As2O3 also induced cancer cell differentiation, it reduced the PCNA expression, and inhibited tumor growth. The tumor growth inhibitory rate in this experimental group was 76.02%. No nephrotoxicity was observed histologically at these dose levels but some pathological changes in liver and cardiac tissues were found. As2O3 proved lethal to the SCID mice at a dose of 10 mg/kg.


CONCLUSIONS
As2O3 has an inhibitory effect on human nasopharyngeal carcinoma xenografts in SCID mice. The mechanism of antitumor activity may be due, at least in part, to the induction of apoptosis and differentiation in cancer cells.
Li
Derui
D
Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China. deruili@pub.shantou.gd.cn
Du
Caiwen
C
Lin
Yingchen
Y
Wu
Mingyao
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D001152:Arsenicals; D006131:Growth Inhibitors; D010087:Oxides; D018809:Proliferating Cell Nuclear Antigen; D000077237:Arsenic Trioxide