Autophagy as a therapeutic target to enhance chemotherapy in oral squamous cell carcinoma
Citation:
Anderson, Aisling, Autophagy as a therapeutic target to enhance chemotherapy in oral squamous cell carcinoma, Trinity College Dublin.School of Dental Sciences, 2021Download Item:
Anderson_Aisling_PhDThesis.pdf (Thesis) 12.81Mb
Abstract:
Oral cancer is the 15th most common cancer worldwide and oral squamous
cell carcinoma accounts for 90% of oral cancer cases. Current therapeutic
interventions for OSCC include surgical intervention with radiation
therapy and chemotherapy used as adjuvant therapies. Chemotherapeutic
intervention alone, is often avoided due to its association with chemoresistance.
This study focuses on the optimisation of chemotherapeutic
interventions to reduce resistance in improve and the patients quality of
life after treatment.
IC50 values for Cisplatin, Carboplatin, 5-fluorouracil and docetaxel were
determined in, Ca9-22, SCC4, TR146 and DOK cell lines, data that is not
readily available in research papers. The induction of autophagy by
chemotherapeutic intervention was also verified in these OSCC cell lines.
Inhibition of cisplatin-mediated autophagy by autophagy inhibitor,
chloroquine, lowered the IC50 of cisplatin OSCC cell lines in a cell type
dependant manner. This increase in cisplatin-mediated cell death was
shown to be linked to mitochondrial dysfunction via alterations to basal
oxygen consumption rate and spare respiratory capacity. By knocking
down P53 in TR146 cells, it was shown that P53- have a lower rate of basal
respiration than P53+ cells.
The data presented in this thesis verify the hypothesis that inhibition of
autophagy can prevent cell survival mechanisms and increase the efficacy
of chemotherapeutic intervention.
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https://tcdlocalportal.tcd.ie/pls/EnterApex/f?p=800:71:0::::P71_USERNAME:ANDERSAIDescription:
APPROVED
Author: Anderson, Aisling
Advisor:
O'Sullivan, JeffreyPublisher:
Trinity College Dublin. School of Dental Sciences. Discipline of Dental ScienceType of material:
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