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.authorGerber, Anthonie
dc.contributor.authorHiss, Donavon C.
dc.date.accessioned2024-03-14T11:51:59Z
dc.date.available2024-03-14T11:51:59Z
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.description.versionPublisher's version
dc.identifier.citationAbrahams, B., Gerber, A., & 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), 3066. https://doi.org/10.3390/ijms25053066
dc.identifier.issn1661-6596 (print)
dc.identifier.issn1422-0067 (online)
dc.identifier.urihttps://doi.org/10.3390/ijms25053066
dc.identifier.urihttp://hdl.handle.net/11660/12466
dc.language.isoen
dc.publisherMDPI
dc.rights.holderAuthor(s)
dc.rights.licensehttps://www.mdpi.com/about/openaccess
dc.subjectbreast cancer
dc.subjecttriple-negative breast cancer (TNBC)
dc.subjectdoxorubicin (Dox)
dc.subjectepidermal growth factor receptor (EGFR) inhibitor (EGFRi)
dc.subjectgrowth inhibition
dc.subjectdrug combination
dc.subjectsynergistic interactions
dc.subjectBliss independence
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:
1.63 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Research Articles (Basic Medical Sciences)