Document Details

Document Type : Thesis 
Document Title :
Studying the Role of BCL2 Inhibitors in Adriamycin Resistant Acute Myeloid Leukemia Cell Lines
دراسة دور مانعات المورثة BCL2 في خطوط الخلايا النخاعية لسرطان الدم الحاد المقاومة لعلاج الادريامايسين
 
Subject : Faculty of Applied Medical Sciences 
Document Language : Arabic 
Abstract : Acute myeloid leukemia (AML) is a clonal disorder of the blood forming cells in which myeloid cells fail to differentiate into functional cells and multiply unstoppably. The standard treatment of AML comprises of high dose chemotherapy with anthracyclines such as adriamycin (Adr) or daunorubicin used in combination with cytarabine (AraC). The outcome of standard AML therapy is highly variable and depends upon the molecular mutational background as well as age of the patients. The major reasons for failure of high dose chemotherapy in AML are drug resistance and treatment related mortality. Resistance to Adriamycin and daunorubicin has been reported in many cancers including AML. Finding new agents that show reversal of drug resistance has been the target of many studies. BCL-2 family of proteins is frequently overexpressed in leukemia leading to resistance of cells to undergo apoptosis. In this study we aimed to test the role of BCL-2 inhibitors on the reversal of Adriamycin resistance. We generated Adriamycin (Adr) resistant cell line from AML cell line K562 and studied the effects of BCL-2 inhibitors (ABT-737, HA14-1, Curcumin and Obatoclax) on the proliferation and the apoptosis of Adr-resistant cells. Cell viability assays were performed to assess the cytotoxicity of drugs by measuring the half maximal inhibitory concentration (IC50). Apoptosis induction was analysed by flow cytometry. Cell viability assays demonstrated that B4 (Adr resistant cells) had 3.2 fold higher IC50 values as compared to the parental K562 cells. We could show that B4 cells accumulated less Adr than the K562 cells which correlated to high expression of multidrug resistant protein ABCB1, indicating efflux of Adr as the main cause of resistance. BCL-2 inhibitors alone showed similar induction of apoptosis on K562 and B4 cells, however, when we investigated BCL-2 inhibitors on modulation of Adr cytotoxicity, we found that ABT-737, HA14-1 and Curcumin but not Obatoclax modulate the IC50 values of Adr. Further studies on interaction of these BCL2 inhibitors and ABCB1 using functional efflux as well as computer aided molecular docking are warranted. 
Supervisor : Prof. Mamdooh Gari 
Thesis Type : Master Thesis 
Publishing Year : 1438 AH
2017 AD 
Co-Supervisor : Dr. Farid Ahmed 
Added Date : Sunday, May 14, 2017 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
تهاني عيادة العصلانيAlaslani, Tahani AyadahResearcherMaster 

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