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The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells
Thesis (MSc)--Stellenbosch University, 2019.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2019
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| _version_ | 1867613785825476608 |
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| access_status_str | Open Access |
| author | Fourie, Carla |
| author2 | Engelbrecht, Anna-Mart |
| author_browse | Engelbrecht, Anna-Mart Fourie, Carla |
| author_facet | Engelbrecht, Anna-Mart Fourie, Carla |
| author_sort | Fourie, Carla |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2019. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/106181 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:41:40.401Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2019 |
| publishDateRange | 2019 |
| publishDateSort | 2019 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/106181 The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells Fourie, Carla Engelbrecht, Anna-Mart Davis, Tanja Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. Breast cancer -- Treatment resistance Breast -- Cancer -- Treatment Chemotherapeutic treatment with Doxorubicin UCTD Thesis (MSc)--Stellenbosch University, 2019. The published article for this Doctoral/Master’s is available at [http://hdl.handle.net/10019.1/123038] ENGLISH 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. AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar 2019-02-19T09:12:44Z 2019-04-17T08:32:57Z 2019-02-19T09:12:44Z 2019-04-17T08:32:57Z 2019-04 Thesis http://hdl.handle.net/10019.1/106181 en_ZA Stellenbosch University 152 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Breast cancer -- Treatment resistance Breast -- Cancer -- Treatment Chemotherapeutic treatment with Doxorubicin UCTD Fourie, Carla The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells |
| title | The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells |
| title_full | The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells |
| title_fullStr | The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells |
| title_full_unstemmed | The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells |
| title_short | The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells |
| title_sort | paracrine effects of fibroblasts on doxorubicin treated breast cancer cells |
| topic | Breast cancer -- Treatment resistance Breast -- Cancer -- Treatment Chemotherapeutic treatment with Doxorubicin UCTD |
| url | http://hdl.handle.net/10019.1/106181 |
| work_keys_str_mv | AT fouriecarla theparacrineeffectsoffibroblastsondoxorubicintreatedbreastcancercells AT fouriecarla paracrineeffectsoffibroblastsondoxorubicintreatedbreastcancercells |