Chloroquine sensitizes MDA-MB-231 cells to osimertinib through autophagy-apoptosis crosstalk pathway

Triple-negative breast cancer (TNBC) is a breast cancer that tests negative for estrogen receptor (ER), progesterone receptors, and human epidermal growth factor receptors 2 (HER2). It is aggressive and invasive in nature and lacks targeted therapy. The EGFR is frequently overexpressed in TNBC, and...

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Bibliographic Details
Published in:Breast cancer targets and therapy 2019-07, Vol.11, p.231-241
Main Authors: Fleisher, Brett, Mody, Hardik, Werkman, Carolin, Ait-Oudhia, Sihem
Format: Article
Language:English
Subjects:
Apoptosis
Autophagic flux
Autophagy
Breast cancer
Cancer
Cancer cells
Cancer therapies
Caspase
Caspase-3
Cell death
Chemotherapy
Chloroquine
Drug interaction
Drug interactions
Drug-Drug interaction
EGFR Inhibitor
Epidermal growth factor
Epidermal growth factor receptors
Epidermal growth factors
ErbB-2 protein
Estrogen receptors
Estrogens
Growth factor receptors
Invasiveness
Kinases
Medical prognosis
Original Research
Osimertinib
Phagocytosis
Phenols (Class of compounds)
Phosphorylation
Progesterone
Progesterone receptors
programed cell death
Sex hormones
Synergy
Targeted cancer therapy
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Summary:Triple-negative breast cancer (TNBC) is a breast cancer that tests negative for estrogen receptor (ER), progesterone receptors, and human epidermal growth factor receptors 2 (HER2). It is aggressive and invasive in nature and lacks targeted therapy. The EGFR is frequently overexpressed in TNBC, and the EGFR-overexpressing TNBC presumably escapes EGFR inhibitor therapy by upregulating autophagy and inhibiting apoptosis. To parse the autophagy-apoptosis crosstalk pathway as a potential targeted therapy in TNBC, the activity of an EGFR inhibitor, osimertinib, alone and in combination with an autophagy inhibitor, chloroquine, was examined in EGFR-overexpressing TNBC cell line, MDA-MB-231. The nature of interaction between both drugs at various concentrations was determined by calculating combination indexes (CI) using CompuSyn software. Temporal changes in the expression of the autophagy marker, LC3B-II, and several apoptosis signaling molecules were measured using Western blot and luminex assay with MAGPIX after exposure to drugs. A synergistic interaction (CI
ISSN:1179-1314
1179-1314
DOI:10.2147/BCTT.S211030