Rohollah Kamyabi - Department of Veterinary Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
Alireza Jahandideh - Department of Veterinary Surgery, Science and Research Branch, Islamic Azad University, Tehran, Iran
Negar Panahi - Department of Veterinary Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
Samad Mohammadnejad - Gene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran

Objective(s): Intolerable side effects and resistance to chemotherapeutic drugs have encouraged scientists to develop new methods of drug combinations with fewer complications. This study aimed to investigate the synergistic effects of quercetin and imatinib encapsulated in chitosan nanoparticles on cytotoxicity, apoptosis, and cell growth of the K۵۶۲ cell line.Materials and Methods: Imatinib and quercetin were encapsulated in chitosan nanoparticles and their physical properties were determined using standard methods and SEM microscope images. BCR-ABL positive K۵۶۲ cells were cultured in a cell culture medium, cytotoxicity of drugs was determined by MTT assay and the effects of nano drugs on apoptosis in cells were investigated by Annexin V-FITC staining. The expression level of genes associated with apoptosis in cells was measured by real-time PCR. Results: The IC۵۰ for the combination of the nano drugs at ۲۴ and ۴۸ hr was ۹.۳۲۴ and ۱۰.۸۶ μg/ml, respectively. The data indicated that the encapsulated form of drugs induced apoptosis more effectively than the free form (P<۰.۰۵). Moreover, the synergistic effect of nano drugs in statistical analysis was proved (P=۰.۰۰۱). The combination of nano drugs resulted in the caspase ۳, ۸, and TP۵۳ genes upregulation (P=۰.۰۰۱).Conclusion: The results of the present study showed that the encapsulated form of imatinib and quercetin nano drugs with chitosan has more cytotoxicity than the free form of the drugs. In addition, the combination of imatinib and quercetin as a nano-drug complex has a synergistic effect on the induction of apoptosis in imatinib-resistant K۵۶۲ cells.

Chitosan, Chronic myeloid leukemia, Imatinib, K۵۶۲, Quercetin