Effects of arsenic trioxide on the cerulein-induced AR42J cells and its gene regulation.

OBJECTIVES: To study the molecular mechanism of arsenic trioxide-induced cell death on cerulein-stimulated AR42J cells. METHODS: AR42J cells were incubated for 24 hours, and cerulein (10 nmol/L) and different concentrations of arsenic trioxide were added for another 24 hours. The cells were collected and analyzed for apoptosis and oncosis by using rhodamine 123 and propidium iodide staining, and the changes in the genes that related to cell death were detected by a gene chip. RESULTS: After cerulein stimulation, apoptosis was significantly increased in the AR42J cells. The addition of arsenic trioxide increased the number of apoptotic cells, and the apoptotic index reached its peak in the 1-micromol/L group. Regarding oncosis, low concentrations of arsenic trioxide (0.5, 1, 2, and 4 micromol/L) reduced the development of oncosis, and in the 2-micromol/L group, it was most significant, whereas high concentration of arsenic trioxide (8 micromol/L) promoted the development of oncosis. A total of 96 genes related to apoptosis were detected, and 36 genes were differentially expressed. CONCLUSIONS: Appropriate concentrations of arsenic trioxide can induce apoptosis in AR42J cells that were induced by cerulein and lead to changes in the expressions of certain genes.