Abstract: BACKGROUND ＆ AIM: To investigate a possible mechanism of arsenic trioxide-induced apoptosis in K562 cells. MATERIAL AND METHODS: The K562 cells were treated with As2O3 at 1, 2, 4, 8 μmol/L. Light and transmission electron microscope were used to examine the morphologic changes of K562 cells every 24 hours. Methyl thiazolyl tetrozolium(MTT) was used to establish the dose-effect curves of cell proliferation and apoptotic rates were measured by flow cytometry(FCM),RT-PCR was used to detect the expression of Evi-1 mRNA and cellular JNK was detected by ELISA. RESULTS: MTT test showed K562 cell proliferation was significantly inhibited by As2O3 in time and dose-dependent fashion. Marked apoptosis was detected by FCM in K562 cells after treatment by As2O3 at 1,2,4, 8 μmol/L and increased in a time-dependent manner within 48 hours and the optimal concentration was 4 μmol/L. As2O3 could down-regulate significantly the expression of Evi-1 mRNA and up-regulate JNK protein in K562 cells in time- and dose-dependent manner. CONCLUSION: As2O3 could obviously inhibit the expression of Evi-1 mRNA and activate JNK signal transduction pathway, which may be a possible mechanism of As2O3 inducing apoptosis in K562 cells.

Key words: arsenic trioxide, chronic myelogenous leukemia cell line, K562, ecotropic virus integration site1, c-jun terminal kinase