Combination treatment with EGFR Inhibitor and doxorubicin synergistically inhibits proliferation of MCF-7 cells and MDA-MB-231 triple-negative breast cancer cells in vitro

Simple item page
dc.contributor.authorAbrahams, Beynon
dc.contributor.authorHiss, Donavon Charles
dc.contributor.authorGerber, Anthonie
dc.date.accessioned2025-01-22T13:19:44Z
dc.date.available2025-01-22T13:19:44Z
dc.date.issued2024
dc.description.abstractThe role of the epidermal growth factor receptor (EGFR) in tumor progression and survival is often underplayed. Its expression and/or dysregulation is associated with disease advancement and poor patient outcome as well as drug resistance in breast cancer. EGFR is often overexpressed in breast cancer and particularly triple-negative breast cancer (TNBC), which currently lacks molecular targets. We examined the synergistic potential of an EGFR inhibitor (EGFRi) in combination with doxorubicin (dox) in estrogen-positive (ER+) MCF-7 and MDA-MB-231 TNBC cell lines. The exposure of MDA-MB-231 and MCF-7 to EGFRi produced an IC50s of 6.03 µM and 3.96 µM, respectively. Dox induced MDA-MB-231 (IC50 9.67 µM) and MCF-7 (IC50 1.4 µM) cytotoxicity. Combinations of EGFRi-Dox significantly reduced the IC50 in MCF-7 (0.46 µM) and MBA-MB 231 (0.01 µM). Synergistic drug interactions in both cell lines were confirmed using the bliss independence model. Pro-apoptotic caspase-3/7 activation occurred in MCF-7 at 0.1–10 µM of EGFRi and dox single treatments, whilst 1 μM dox yielded a more potent effect on MDA-MB-231. EGFRi and Dox individually and in combination downregulated the EGFR gene expression in MCF-7 and MDA-MB-231 (p < 0.001). This study demonstrates EGFRi’s potential for eliciting synergistic interactions with dox, causing enhanced growth inhibition, apoptosis induction, and downregulation of EGFR in both cell lines.
dc.identifier.citationAbrahams, B., Gerber, A. and Hiss, D.C., 2024. Combination Treatment with EGFR Inhibitor and Doxorubicin Synergistically Inhibits Proliferation of MCF-7 Cells and MDA-MB-231 Triple-Negative Breast Cancer Cells In Vitro. International Journal of Molecular Sciences, 25(5), p.3066.
dc.identifier.urihttps://doi.org/10.3390/ijms25053066
dc.identifier.urihttps://hdl.handle.net/10566/19923
dc.language.isoen
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)
dc.subjectBliss independence
dc.subjectBreast cancer
dc.subjectDoxorubicin (Dox)
dc.subjectDrug combination
dc.subjectEpidermal growth factor receptor (EGFR) inhibitor (EGFRi)
dc.titleCombination treatment with EGFR Inhibitor and doxorubicin synergistically inhibits proliferation of MCF-7 cells and MDA-MB-231 triple-negative breast cancer cells in vitro
dc.typeArticle

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
abrahams_combination_treatment_with_egfr_inhibitor_2024.pdf
Size:
2.48 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Research Articles (Medical Bioscience)