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

Abrahams, BeynonGerber, AnthonieHiss, Donavon C.2024-03-142024-03-142024Abrahams, 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/ijms250530661661-6596 (print)1422-0067 (online)https://doi.org/10.3390/ijms25053066http://hdl.handle.net/11660/12466The 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.enbreast cancertriple-negative breast cancer (TNBC)doxorubicin (Dox)epidermal growth factor receptor (EGFR) inhibitor (EGFRi)growth inhibitiondrug combinationsynergistic interactionsBliss independenceCombination treatment with EGFR inhibitor and doxorubicin synergistically inhibits proliferation of MCF-7 cells and MDA-MB-231 triple-negative breast cancer cells In VitroArticleAuthor(s)https://www.mdpi.com/about/openaccess