Sekhoacha, M. P.Abrahams, B. R.Ngesi, Nandi2024-07-192024-07-192023http://hdl.handle.net/11660/12712Dissertation (M.Med.Sc.(Pharmacology))--University of the Free State, 2023𝗜𝗻𝘁𝗿𝗼𝗱𝘂𝗰𝘁𝗶𝗼𝗻: Prostate cancer (PCa) is the second-most diagnosed cancer among men worldwide, and the foremost male malignancy in South Africa. Various therapies are used in the treatment of PCa patients. However, despite advances in cancer therapy, treatment failures still lead to the advancement of the disease, relapse, and ultimately mortality. Chemotherapy is the treatment of choice for metastatic PCa, but it is challenged by multidrug resistance (MDR) of cancer cells. Various mechanisms participate in the MDR of cancer cells, including an increase in drug efflux facilitated by members of the ATPbinding cassette (ABC) transporters such as ATP-binding cassette sub-family C (ABCC1) / multidrug resistance-associated protein (MRP1), ABCC2/MRP2, and ABCC10/MRP7. Therefore, discovering drug resistance biomarkers and mechanisms is essential in both understanding and combating chemoresistance. This study identifies cellular drug transporter genes (ABCC1, ABCC2, and ABCC10) as possible targets for the prediction of docetaxel treatment outcomes in PCa patients. 𝗣𝘂𝗿𝗽𝗼𝘀𝗲: The aim of this study was to investigate whether a correlation exists between the expression levels of ABCC1, ABCC2, and ABCC10 transporter genes and good versus (vs) poor responses to chemotherapy. Methods: A total of nine Formalin-Fixed Paraffin-Embedded (FFPE) tissue biopsies of PCa patients were obtained from National Health Laboratory Service, Universitas academic hospital, and divided into two categories, good and poor responders. RNA and proteins were extracted from the FFPE tissues, quantified, and evaluated using quantitative RT-PCR and western blot. 𝗥𝗲𝘀𝘂𝗹𝘁𝘀: quantitative RT-PCR shows that ABCC1/MRP1, ABCC2/MRP2, and ABCC10/MRP7 were expressed in the good and poor responder categories of PCa patients. In the good responder category, 50 % of the patients showed elevated expression levels of ABCC1/MRP1 and ABCC10/MRP7 in the normal sections compared to their tumour sections. The expression level of ABCC2/MRP2 was elevated in 75 % of the patients’ normal sections in comparison to their tumour sections. Moreover, in the poor responder category, 80 % of the patients showed elevated expression of ABCC1 in the tumour sections compared to the normal sections, and 60 % of patients showed elevated expression levels of ABCC10 in the tumour sections compared to their normal sections. The expression levels of ABCC2 in the tumour and normal sections of patients in this category of poor responders, could not be compared because the expression levels of ABCC2 could not be determined in 50 % of the patient samples. The average expression levels of ABCC1 and ABCC10 were upregulated in the tumour sections of patients in the poor responder category but were deregulated in the tumour sections of patients in the good responder category. Additionally, ABCC1, ABCC2, and ABCC10’s average expression levels were upregulated in the normal sections of patients in the good responder category and deregulated in the normal sections of patients in the poor responder category. 𝗖𝗼𝗻𝗰𝗹𝘂𝘀𝗶𝗼𝗻𝘀: The results suggest that a correlation exists between the expression levels of ABCC1, ABCC2, and ABCC10 and drug resistance reported in the poor responder category. Also, the detection of these transporter genes could potentially be used as indicators of possible docetaxel treatment outcomes.enProstate cancerchemoresistancedocetaxelABC-transportersFFPE tissueRNA extractionprotein extractionquantitative RT-PCRprotein stainingwestern blotDissertationUniversity of the Free State