BRADFORD SCHOLARS

    • Sign in
    View Item 
    •   Bradford Scholars
    • University of Bradford eTheses
    • Theses
    • View Item
    •   Bradford Scholars
    • University of Bradford eTheses
    • Theses
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Bradford ScholarsCommunitiesAuthorsTitlesSubjectsPublication DateThis CollectionAuthorsTitlesSubjectsPublication Date

    My Account

    Sign in

    HELP

    Bradford Scholars FAQsCopyright Fact SheetPolicies Fact SheetDeposit Terms and ConditionsDigital Preservation Policy

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    The effect of RAN inhibition on human colorectal cancer cells (CRC)

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    View/Open
    PhD Thesis (4.753Mb)
    Download
    Publication date
    2020
    Author
    Elrewey, Hussein A.S.
    Supervisor
    McLean, Samantha L.
    Kantamneni, Sriharsha
    El-Tanani, Mohamed
    Morgan, Richard
    Keyword
    Human colorectal cancer
    Metastasis
    K-Ras mutation
    Pten deletion
    Mebendazole (MBZ)
    Repurposing mebendazole
    Ran inhibition
    Western blot
    Polymerase chain reaction
    Colony formation
    Invasion
    Migration
    Show allShow less
    Rights
    Creative Commons License
    The University of Bradford theses are licenced under a Creative Commons Licence.
    Institution
    University of Bradford
    Department
    Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences
    Awarded
    2020
    
    Metadata
    Show full item record
    Abstract
    Colorectal cancer (CRC) is the third most widespread and fourth most fatal malignancy disease. The CRC from a primary site can spread to other tissues, forming secondary tumours. CRC can metastasise to the liver through the effect of K-Ras and Pten mutation (Mt.) (Abbas et al. 2020). This study aimed to assess the hypothesis that the Ran inhibitor mebendazole MBZ reduces cell invasion and metastasis of CRC. I have investigated MBZ effect on the CRC isogenic human cell lines with specific mutations (HCT-116 K-Ras, DLD-1 K-Ras and Pten deletion and wild type HCT-116 and DKO-3. I used qRT-PCR and western blotting to identify expression levels of various genes and signalling molecules after treatment with 0.5 mM MBZ. In addition, several assays were performed to investigate MBZ effect on biological properties of the cells such as proliferation, migration, invasion, and colony formation. MBZ downregulated Ran and induced apoptosis through inhibition of Bcl-2 expression as well as inducing caspase -3, -7, -9 and PARP cleavage. Moreover, MBZ showed an effect on immune response by down regulating C5a, IL-1ß and IL-1α analysed at mRNA level. When treated with MBZ, the migration, invasion and colony formation abilities of HCT-116 K-Ras Mt., DLD-1 K-Ras Mt. and HCT-116 Pten-/- were significantly reduced compared to a control treated cell line. This was also the case with wild type cell lines such as HCT-116 and DKO-3. Furthermore, signalling molecules such as p- Erk 1/2 and p- Akt were upregulated after MBZ treatment and exert inhibition on Akt 1/2/3 and VEGFR1/2 mRNA levels. In conclusion; MBZ which is a Ran inhibitor, has significantly reduced proliferation, colony formation, and migration in colorectal cell lines with K-Ras and Pten gene deletion compared to wild type cells in a dose-dependent manner. This work paves the way to clinical validation of MBZ as a combination therapy for reducing the invasion of CRC cells.
    URI
    http://hdl.handle.net/10454/19110
    Type
    Thesis
    Qualification name
    PhD
    Collections
    Theses

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.