Cervical cancer is the third most commonly diagnosed cancer globally and it has also been
identified as one of three AIDS defining malignancies. Highly active antiretroviral therapy
(HAART) is a combination of three or more antiretroviral drugs which are classified as
nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse
transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). HAART has been shown to
play a significant role in reducing the incidence of some AIDS defining malignancies,
although its effect on cervical cancer is still unclear. It is hypothesized that HAART might
reduce cancer risk by interacting with different signalling molecules and pathways that are
involved in cancer in order to induce cell death and thus inhibit cell proliferation. The broader
aim of this study was to understand the relationship between cervical cancer and HAART.
This was achieved by studying the expression of key signalling molecules in cancer; MUC1
and NFkB (P65) and morphological features using scanning electron microscopy following
24 hour treatment of a cervical cancer cell line, HCS-2 with drugs which are commonly used
as part of HAART; Emtricitabine (FTC), Tenofovir disoproxil fumarate (TDF), Efavirenz
(EFV), Atripla combination (ATP) and Kaletra combination (LPV/r) at their clinical plasma
concentrations. Quantitative real time polymerase chain reaction (qPCR) was used in order to
study the gene expression of MUC1 and P65 and the data was analysed using the 2-ΔΔCT
method to calculate fold change. The statistical analysis was conducted using JMP 11
software. MUC1 and P65 gene expression was reduced following drug treatment. Protein
expression was studied by means of Immunofluorescence and MUC1 and P65 protein
expression was reduced following drug treatment. Scanning electron microscopy revealed
characteristic features of apoptotic cell death such as loss of cell contacts, reduced density
and size of microvilli, increase in surface blebbing and budding and degradation of apoptotic
bodies following treatment with all the drugs. In conclusion, the drugs used in this study
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/17416 |
| Date | 13 April 2015 |
| Creators | Thabethe, Kutlwano Rekgopetswe |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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