DOI
https://doi.org/10.25772/MX6H-YW25
Author ORCID Identifier
0000-0002-5500-7555
Defense Date
2019
Document Type
Thesis
Degree Name
Master of Science
Department
Physiology and Biophysics
First Advisor
Dr. Rakesh C. Kukreja
Second Advisor
Dr. Anindita Das
Third Advisor
Dr. Lei Zhou
Abstract
The field of cancer research has grown immensely in recent decades and has led to a better understanding of the causes of the disease, as well as greatly improved treatment for various types of cancers, especially breast cancer. One of the most effective treatments involves the chemotherapeutic drug doxorubicin (DOX). DOX is an effective tool against all types of breast cancer, especially against triple negative breast cancer. However, DOX causes adverse side effects that include damage to the heart and skeletal muscle, particularly above specific cumulative doses. Recent evidence suggests that embryonic stem cell-derived (ES) exosomes, nanoscale extracellular vesicles that carry proteins, messenger RNA, and microRNAs, may be able to mitigate some of the cardio- and cytotoxic effects of DOX without reducing its efficacy.
The present study examined the effects of combined treatment with DOX (1 μM) and ES exosomes (10 μg/mL) on three cancer cell lines, MCF7, MDA-MB-231, and MDA-MB-468. The DOX/ES exosomes treatment increased cell death and increased apoptosis specifically compared to control, as measured via dye exclusion assay and flow cytometry. The treatment also decreased cell growth compared to control, as measured via MTS cell proliferation assay. In addition, DOX/ES exosomes treatment also increased expression of pro-apoptotic Bax while decreasing the expression of anti-apoptotic Bcl-2, as measured via Western blot. Finally, the DOX/ES exosomes treatment decreased expression of miR-200c, a microRNA associated with preventing epithelial-mesenchymal transition, a process that is integral to metastasis.
Although increased cell death and apoptosis and decreased cell proliferation implies that the DOX/exosomes treatment is effective against cancer, the decrease in miR-200c expression may suggest the opposite and will be investigated further in future studies. Even so, the results of this study suggest that exosomes may be an important component to reduce the harmful effects of cancer treatment in the future.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
7-22-2019