Combination effect of doxorubicin and HIF inhibitor on MCF-7 CD44+/CD24- subpopulation cells in hypoxic condition
DOI:
https://doi.org/10.1590/s2175-97902020000318754%20Keywords:
FM19G11, Combination Index, Hypoxia-induced factor, Cytotoxicity, Cancer stem cellsAbstract
Hypoxia-inducible factors (HIFs) and cancer stem cells (CSCs) are two challenging causes of
radiotherapy and chemotherapy resistance, leading to most cases of failure and recurrence in breast
cancer therapy. This study was conducted to investigated the inhibitory effect of combination
therapy with doxorubicin (an anthracycline) and FM19G11 (an HIF inhibitor) on MCF-7 cells and
their CSC-like cells (CSC-LCs). MCF-7 CSC-LCs with a CD44+
/CD24-
phenotype were sorted and
characterized by flow cytometry. A combination of doxorubicin and FM19G11 caused more cytotoxic
effects on MCF-7 and CSC-LCs compared to doxorubicin monotherapy. The largest synergistic effect
was observed in CSC-LCs under hypoxic conditions; however, MCF-7 cells showed no synergism in
normoxic conditions. The administration of doxorubicin and FM19G11 induced late apoptotic and
necrotic cell death in MCF-7 and CSC-LCs. Additionally, G2 phase arrest was observed in both
cells. Our results demonstrated that co-administration of FM19G11 and doxorubicin had a synergistic
effect in hypoxia and improved drug resistance in breast cancer stem cells.
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