Nrf2 Inhibitor, Brusatol in Combination with Trastuzumab Exerts Synergistic Antitumor Activity in HER2-Positive Cancers by Inhibiting Nrf2/HO-1 and HER2-AKT/ERK1/2 Pathways
Brusatol exhibited antitumor activity in combination with trastuzumab in a synergistic manner on HER2-positive BT-474 and SK-OV-3 cells. (a) BT-474, SK-OV-3, and SK-BR-3 cells were treated with trastuzumab and brusatol as single agents and in combination with trastuzumab in a dose range for 2 days. Points, mean of 3 independent CCK-8 assays; bars, SD. ,,. (b) The synergistic effect of trastuzumab in combination with brusatol was evaluated on the growth of BT474, SK-OV-3, or SK-BR-3 cell line. Combination index (CI) values were calculated at the drug concentration of trastuzumab (12.5 μg/mL) plus brusatol (2.5 μM), trastuzumab (25 μg/mL) plus brusatol (5 μM), and trastuzumab (50 μg/mL) plus brusatol (10 μM) using the Chou-Talalay method. Drug synergy, addition, and antagonism are defined by CI values less than 1.0, equal to 1.0, or greater than 1.0, respectively.
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