Effect of As_2S_2 combination with imatinib on the apoptosis of chronic myeloid leukemic cells

Objective To observe the effect of As2S2 combined with imatimib (STI571) on the apoptosis of chronic myeloid leukemic (CML)cells. Methods Cell apoptosis was assessed by MTT proliferation inhibition test, trypan blue exclusion cell count, Giemsa stain cell morphology and Annexin V flow cytometry, expression of bcr-abl mRNA was determined by RT-PCR, and expression of BCR-ABL was assessed by Western blot.; cytochrome C (cyto C) and caspase were also assessed. The effect of As2S2, STI571 and As2S2 combined with STI571 on STI571 sensitive cell line K562S and STI 571 resistant cell line K562R was appraised by the abovementioned parameters. Results As2S2 2.5 μmol/L plus STI571 0.25 μmol/L or As2S2 4 μmol/L plus STI571 8 μmol/L had obvious synergistic growth inhibiting effect and apoptosis promoting effect on both the K562S and K562R cell lines. Combined use of As2S2 and STI571 had no significant effect on the expression of bcr-abl mRNA, however, the BCR-ABL expression decreased significantly in K562S cells and slightly in K562R cells. Furthermore, the combined use of As2S2 and STI571 enhanced the release of cyto C and downregulated the precursors of caspase 9 and caspase 3. Conclusions Combined use of As2S2 and STI571 had significant synergistic growth inhibiting effect and apoptosis promoting effect on K562S and K562R cells. This effect may be mainly through the decrease of BCR-ABL, the release of cyto C and the downregulation of expression of precursors of caspase 9 and caspase 3, promoting the apoptosis of CML cells.