Dynamic interactions between skeletal muscle and breast cancer cells following chemotherapeutic treatment.
Degree: MSc, Physiological Sciences, 2019, Stellenbosch University
ENGLISH ABSTRACT: Background: Breast cancer is the most common cancer found among women of South
Africa with the prominent effective form of treatment being chemotherapy. Many cancer
patients receiving chemotherapeutic treatment experience skeletal muscle wasting,
however, the contribution of muscle wasting to the metastatic properties of breast cancer
and response to current treatment strategies has not yet been fully investigated. The aims of
this study were to investigate the reciprocal interactions between mouse breast cancer cells
(E0771) and mouse myotubes (C2C12) as well as the effects of doxorubicin (DXR) on these
Methods: Conditioned media was collected from two separate cycles. The initial cycle of
conditioned media was collected from E0771 breast cancer cells after treatment with/without
1.6 μM of DXR. Myotubes were then treated with/without DXR as well as conditioned media
collected during the initial cycle from the E0771 cells. A new series of E0771 cells were then
treated with/without DXR as well as with the second cycle of conditioned media collected
from the myotubes. Mitochondrial integrity of myotubes was investigated using MitoSOX™
stain analysis while myotube cell viability and integrity was assessed using a Cell Tracker™
stain analysis. Cell viability of E0771 cells was assessed with an MTT assay and the
migratory properties (wound closure) using a migration scratch assay. Western blot analyses
were used to determined alterations in proliferation, apoptotic, and epithelial-mesenchymal
transition (EMT) signaling pathways.
Results: Treatment of myotubes with 1.6 μM of DXR significantly induced mitochondrial
ROS production (5.580 ± 0.4, p<0.001) when compared to Control but myotube integrity was
maintained. Treatment of E0771 cells with 1.6 μM of DXR compared to Control significantly
decreased cell viability (60.354% ± 1.237, p<0.001), significantly increased the
phosphor/total ERK expression ratio (3.946 ± 0.520, p<0.001), and significantly decreased
the cleaved/total PARP expression ratio (0.651 ± 0.027, p<0.001). Additionally, a significant
increase in the percentage of wound closure was also observed in the DXR group (16.049%
± 1.11, p<0.01) compared to Control after 24-hours. E0771 cells treated with myotube
conditioned media after treatment of DXR (C.DXR), induced a significant decrease in
expression of the cleaved/total PARP ratio (0.662 ± 0.097, p<0.01) as well as a significant
difference in percentage of wound closure (17.19 ± 0.758, p<0.001) compared to C.Control.
Following treatment of the E0771 cells with myotube conditioned media, harvested after the treatment of conditioned media from DXR treated E0771 cells (C.C.DXR), a significant
increase in cell viability (121.743% ± 3.442, p<0.05) when compared to C.C.Control.
Additionally, comparison of C.C.DXR to C.C.Control observed a significant decrease in
expression of total Akt (65.554% ± 17.55, p<0.05), MCM2 (55.167% ± 14.64, p<0.05), and
the cleaved/total PARP ratio (0.456 ± 0.111, p<0.001)…
Advisors/Committee Members: Engelbrecht, Anna-Mart, Isaacs, Ashwin, Davis, Tanja, Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences..
Subjects/Keywords: Breast – Cancer – Treatment; Chemotherapeutic treatment; Skeletal muscle wasting; Skeletal muscles and chemotherapy; UCTD
to Zotero / EndNote / Reference
APA (6th Edition):
Conradie, D. (2019). Dynamic interactions between skeletal muscle and breast cancer cells following chemotherapeutic treatment. (Masters Thesis). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/106205
Chicago Manual of Style (16th Edition):
Conradie, Daleen. “Dynamic interactions between skeletal muscle and breast cancer cells following chemotherapeutic treatment.” 2019. Masters Thesis, Stellenbosch University. Accessed November 14, 2019.
MLA Handbook (7th Edition):
Conradie, Daleen. “Dynamic interactions between skeletal muscle and breast cancer cells following chemotherapeutic treatment.” 2019. Web. 14 Nov 2019.
Conradie D. Dynamic interactions between skeletal muscle and breast cancer cells following chemotherapeutic treatment. [Internet] [Masters thesis]. Stellenbosch University; 2019. [cited 2019 Nov 14].
Available from: http://hdl.handle.net/10019.1/106205.
Council of Science Editors:
Conradie D. Dynamic interactions between skeletal muscle and breast cancer cells following chemotherapeutic treatment. [Masters Thesis]. Stellenbosch University; 2019. Available from: http://hdl.handle.net/10019.1/106205