Background: Leukemia is a malignant and progressive disease. Over-expression of inhibitors of apoptosis proteins (IAPs), such as survivin and its anti-apoptotic variants, including sur-ΔEx3, is the main cause of resistance to apoptotic effects of chemotherapy drugs. In the present study, the effects of CBX on apoptosis and expression level of survivin and sur-ΔEx3 and K562 cells (experimental model of chronic myeloid leukemia) were investigated. Materials and Methods: In this experimental study, human K562 cells were cultured and exposed to CBX. Trypan blue exclusion test was used to evaluate growth inhibitory and viability effects of the drug. Fluorescent microscopy (acridine orange/ ethidium bromide double staining) and DNA electrophoresis were applied to the study of apoptosis. The expression level of survivin and sur-ΔEx3 was studied by semiquantative RT- PCR. Results: The results showed that after the 48 h treatment of K562 cells with 150 µM CBX, significant growth inhibitory and apoptotic effects (up to 50%) were induced. In addition, after 2-4 h of treatment with CBX (150 µM), down-regulation of survivin and sur-∆Ex3 were observed. However, the expression level of survivin and sur-ΔEx3 increased to the level of control cells with longer treatment times (6-12 h). Conclusion: Noticing the apoptotic and down-regulatory effects of CBX on survivin and sur-∆Ex3 expression, this drug can be used as a potential candidate for further studies on CML treatment, especially for inhibition of drug resistance in leukemia cells.

Keywords: Apoptosis, Carbenoxolone, Drug Resistance, K562, Leukemia, Survivin

Full-Text [PDF 2279 kb]   (2665 Downloads)