Document Details

Document Type : Thesis 
Document Title :
Effect of inhibitors (PP242), PKI402 and (MTOR) in their combination with MEK cytometry on cancer cell cells
تأثير مثبطات (PP242) و (PKI402) و (MTOR) في اتحادها مع مثبط (MEK) سليومتنب على خلايا النخاع السرطانية
 
Subject : Faculty of Applied Medical Sciences 
Document Language : Arabic 
Abstract : Acute myeloid leukaemia (AML) is a type cancer in which myeloid cells proliferate unstoppably and lose the ability to differentiate into functional cells. AML patients generally have a poor outcome with standard chemotherapy and are associated with high relapse rates. Therefore, new therapies with lower toxicities and higher cure rates, such as targeted therapy must be tested. Cellular signaling pathways such as the mammalian target of rapamycin (mTOR) pathway and the MAPK/ERK pathway are often hyper-activated or deregulated due to genetic abnormalities in AML. Inhibitors of mTOR and MAPK/ERK pathways show promising results in different types of malignancies. In the current study we aimed to combine PI3K/mTOR inhibitors (PKI-402 and PP242) with a MAPK/ERK pathway inhibitor (Selumetinib; SEL) on AML cell lines and patient samples. Cell proliferation assays were performed to assess the effect of the drug. The Chou-Talalay multi-drug combination method, was used to determine the combination index (CI) values which measure the interaction between two drug combinations. Drug treated cells were analyzed by flow cytometry to assay apoptosis and cell cycle proliferation. In our cell proliferation experiments PKI-402 and PP242 demonstrated synergistic effects when combined with SEL in HL60 and NB4. Increased apoptosis was observed when we combined PP242 or PKI-402 with SEL. The mTOR inhibitor alone did not induce apoptosis in primary cells. Primary patient samples showed varying results with the mTOR- MAPK/ERK inhibitor combinations. In conclusion, the combination of mTOR and MAPK/ERK inhibitors represents a potentially promising approach in the treatment of AML. A larger number of primary AML patient samples is needed to evaluate the effect of the combination. The mechanism under which these two pathways interact needs to be demonstrated. An extension of this study in preclinical animal models will be of great value. 
Supervisor : Dr. Adel Mohammed Abunada 
Thesis Type : Master Thesis 
Publishing Year : 1438 AH
2017 AD 
Co-Supervisor : Dr. Farid Ahmed Yassin 
Added Date : Sunday, April 16, 2017 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
منال عبد الغفور أسرارAsrar, Manal Abdul GhafoorResearcherMaster 

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