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en AMG-232, a New Inhibitor of MDM-2,Enhance Doxorubicin Efficiency in Pre-B Acute Lymphoblastic Leukemia Cells زیست شناسی ملکولی Molecular Biology مقالات اصلی Original Article <div style="text-align: justify;">Background: Doxorubicin (DOX)-induced cardiotoxicity appears to be a growing concern for extensive use in acute lymphoblastic leukemia (ALL). The new combination treatment strategies, therefore might be an effective way of decreasing its side effects as well as improving efficacy. AMG232 (KRT-232) is a potential MDM-2 inhibitor, increasing available p53 through disturbing p53-MDM-2 interaction. In this study, we examined the effects of AMG232 on DOX-induced apoptosis of NALM-6 cells. Methods: The anti-leukemic effects of Doxorubicin on NALM-6 cells, either alone or in combination with AMG232, were confirmed by MTT assay, Annexin/PI apoptosis assay, and cell cycle analysis. Expression of apoptosis and autophagy-related genes were further evaluated by Real time-PCR method. To investigate the effect of AMG232 on NALM-6 cells, the activation of p53, p21, MDM-2, cleaved Caspase-3 proteins was evaluated using western blot analysis. Results: The results showed that AMG232 inhibition of MDM-2 enhances Doxorubicin-induced apoptosis in NALM-6 cells through caspase-3 activation in a time and dose-dependent manner. Furthermore, cotreatment of AMG232 with Doxorubicin hampered the transition of NALM-6 cells from G1 phase through increasing p21 protein. In addition, this combination treatment led to enhanced expression of apoptosis and autophagy-related genes in ALL cell lines. Conclusions: The results declared that AMG232 as an MDM-2 inhibitor could be an effective approach to enhance antitumor effects of Doxorubicin on NALM-6 cells as well as an effective future treatment for ALL patients.</div> Acute Lymphoblastic Leukemia, AMG 232, Autophagy, Doxorubicin, p53. 111 124 http://rbmb.net/browse.php?a_code=A-10-920-1&slc_lang=en&sid=1 Abbas Ghotaslou 100319475328460012356 100319475328460012356 No Department of Hematology and Blood Banking, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran Amir Samii 100319475328460012357 100319475328460012357 No Department of Hematology and Blood Banking, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran Hassan Boustani 100319475328460012358 100319475328460012358 No Department of Hematology and Blood Banking, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran Omid Kiani Ghalesardi 100319475328460012359 100319475328460012359 No Department of Hematology and Blood Banking, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran Minoo Shahidi shahidi.m@iums.ac.ir. 100319475328460012360 100319475328460012360 Yes Department of Hematology and Blood Banking, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran & Cellular and Molecular Research Center (CMRC), Iran University of Medical Sciences, Tehran, Iran.