The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells

dc.contributor.advisorEngelbrecht, Anna-Marten_ZA
dc.contributor.advisorDavis, Tanjaen_ZA
dc.contributor.authorFourie, Carlaen_ZA
dc.contributor.otherStellenbosch University. Faculty of Science. Dept. of Physiological Sciences.en_ZA
dc.descriptionThesis (MSc)--Stellenbosch University, 2019.en_ZA
dc.description.abstractENGLISH ABSTRACT: Introduction: Breast cancer is frequently diagnosed in women in both developed and developing countries and poses a major health problem throughout the world. The current standard treatment for breast cancer patients is radiation, surgery and chemotherapy or a combination of surgery with chemotherapy. The unresponsiveness of cancer cells to chemotherapeutics, however, is still a main concern. During chemotherapeutic treatment with Doxorubicin, normal and healthy neighbouring cells are also damaged. Apoptotic or senescent fibroblasts in the tumour microenvironment can then secrete a variety of bioactive molecules which promote tumour growth, metastasis and drug resistance. Methods: Mouse embryonic fibroblasts (MEFs) were cultured and treated with Doxorubicin to induce apoptosis and senescence respectively. An SA-ß-gal stain was used to determine the number of senescent cells in the cell population and expression of apoptotic and senescent markers were determined through western blotting. Conditioned media was collected from the MEFs after apoptosis and senescence induction and used to assess the paracrine effects between fibroblasts and E0771 cells. Results and discussion: Doxorubicin (1 μM) was able to significantly induce apoptosis in MEFs after 24 hours. During senescence induction, 2 μM of Doxorubicin treatment for 4 hours was unable to induce 80% of senescence in the MEF population. The western blot analyses show that the expression of many apoptosis and senescence markers significantly increased or decreased after Doxorubicin treatment. Furthermore, the results indicate that senescent fibroblasts (56%) were able to significantly increase cell viability in E0771 cells following treatment with Doxorubicin. Conclusion: Our results highlight the fact that the tumour microenvironment is extremely complex and how important it is that chemotherapeutic agents such as Doxorubicin should specifically target cancer cells. Once healthy, neighbouring stromal cells such as fibroblasts are affected by chemotherapeutic agents, they have the ability to secrete paracrine factors that enhance breast cancer growth and induce therapeutic resistance by evading cell death.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Geen opsomming beskikbaaraf_ZA
dc.format.extent152 pages : illustrationsen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.subjectBreast cancer -- Treatment resistanceen_ZA
dc.subjectBreast -- Cancer -- Treatmenten_ZA
dc.subjectChemotherapeutic treatment with Doxorubicinen_ZA
dc.titleThe paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cellsen_ZA
dc.rights.holderStellenbosch Universityen_ZA

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