Inhibition of Growth of Human Nasopharyngeal Cancer Xenografts in Scid Mice by Arsenic Trioxide

Abstract

Aims and background

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.

Conclusion

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.